Elucidation of the Anti-Lung Cancer Mechanism of Xiao'ai Jiedu Prescription Based on Network Pharmacology and Molecular Docking.

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

Aitongping patch could alleviate cancer pain via suppressing microglia activation and modulating the miR-150-5p/CXCL12 signaling.

PURPOSE: We aimed to investigate the pharmacological effects and mechanisms of the Aitongping formula for treating cancer pain. METHODS: We enrolled 60 cancer patients with Numeric Rating Scale above 4 and grouped them randomly as a Control group (N = 30) and a Patch group (N = 30). We also established bone cancer mice models via tumor implantation. And the animal groups were established as a Sham group, a tumor cell implantation (TCI) group, a TCI + Patch group, and a Patch group. RESULTS: After the validation of successful tumor implantation, we identified candidate miRNAs and genes that were dysregulated in TCI mice and compared their expressions between different mice groups. We also observed the effect of Aitongping patch in vitro in mice primary microglia. The time to disease progression and cancer stability were prolonged by Aitongping patch in cancer patients. And the daily morphine dose was lower, and patients' quality of life was improved in the Patch group. Moreover, Aitongping patch alleviated cancer pain and inhibited microglia activation after the successful implantation of bone tumor in TCI mice. We also observed the dysregulation of miR-150-5p and chemokine CXC motif ligand 12 (CXCL12) mRNA in TCI mice. And CXCL12 was found to be targeted by miR-150-5p. Aitongping patch was found to upregulate miR-150-5p and downregulate CXCL12 in vivo and in vitro. CONCLUSION: Aitongping patch could alleviate cancer pain via suppressing microglia activation, and the downregulation of miR-150-5p, as well as the upregulation of CXCL12 mRNA and protein, induced by tumor implantation or lipopolysaccharide stimulation, was restored by Aitongping treatment.

Maimendong and Qianjinweijing Tang combined with cisplatin suppressed lung cancer through targeting lncRNA-p21.

ETHNOPHARMACOLOGICAL RELEVANCE: Maimendong and Qianjinweijing Tang (Jin formula) is a traditional Chinese medicine formula that has been proven effective in the treatment of lung cancer in long-term clinical practice. AIM OF THE STUDY: To evaluate the anti-tumor effects of Jin formula combined with cisplatin (JIN + DDP) in vivo and in vitro, as well as to explore the role of long non-coding RNA (lncRNA) in the anti-lung cancer mechanism of its action. MATERIALS AND METHODS: A Lewis lung cancer model was established in C57 BL/6 mice to study the in vivo anti-tumor effect of Jin formula combined with cisplatin. TUNEL staining and western blot were applied to study the effects of Jin formula combined cisplatin on apoptosis. The in vitro anti-cancer function of Jin formula combined with cisplatin was explored by cell viability assay, flow cytometry, wound healing assay and transwell assay. The changes in lncRNA expression profiles were determined by lncRNA microarray, and the differentially expressed lncRNA-p21 was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. The expression differences of lncRNA-p21 in tumor and normal tissues were analyzed by bioinformatics, and the expression differences of lncRNA-p21 in tumor cells and normal cells were detected by qRT-PCR. The role of lncRNA-p21 in the anti-cancer effect of Jin formula combined cisplatin was investigated by knockdown or overexpression of lncRNA-p21 and a series of cell experiments. The expression of MAPK pathway-related proteins was analyzed by western blot. RESULTS: Jin formula combined with cisplatin (JIN + DDP) can suppress tumor growth and promote apoptosis in Lewis lung cancer mouse model. LncRNA-p21 was significantly up-regulated in the JIN and JIN + DDP groups, and the expression of lncRNA-p21 in lung cancer tissues and cells was lower than that in normal tissues and cells. In vitro, JIN + DDP significantly induced apoptosis and inhibited the proliferation, migration, and invasion of H460 and H1650 lung cancer cells. The above effects can be enhanced by the overexpression of lncRNA-p21 and eliminated by knock-down of lncRNA-p21. Further studies revealed that JIN + DDP inhibited the expression of mitogen-activated protein kinase (MAPK) pathway-related proteins, whereas knock-down of lncRNA-p21 abrogated the inhibition of the MAPK signaling pathway. CONCLUSIONS: This study showed that Jin formula combined with cisplatin could effectively inhibit the progression of lung cancer partially through targeting lncRNA-p21.

Noninvasive radiomic analysis of enhanced CT predicts CTLA4 expression and prognosis in head and neck squamous cell carcinoma.

Developing a radiomic model to predict CTLA4 expression levels and assessing its prognostic accuracy for patients. Medical imaging data were sourced from the TCIA database, while transcriptome sequencing data were derived from the TCGA database. We utilized a linear kernel SVM algorithm to develop a radiomic model for predicting CTLA4 gene expression. We then assessed the model's clinical relevance using survival and Cox regression analyses. Performance evaluations of the model were illustrated through ROC, PR, calibration, and decision curves. (1) Bioinformatics analysis: Kaplan-Meier curves indicated that increased CTLA4 expression correlates with enhanced overall survival (OS) (p < 0.001). Both univariate and multivariate analyses revealed that high CTLA4 expression served as a protective factor for OS (HR = 0.562, 95% CI 0.427-0.741, p < 0.001). (2) Radiomics evaluation: the ROC curve demonstrated that the AUC for the SVM radiomics model was 0.766 in the training set and 0.742 in the validation set. The calibration curve affirmed that the model's prediction probability for high gene expression aligns with the actual outcomes. Furthermore, decision curve analysis (DCA) indicated that our model boasts robust clinical applicability. CTLA4 expression level serves as an independent prognostic factor for HNSCCs. Using enhanced CT images, the SVM radiomic model effectively predicts CTLA4 expression levels. As a result, this model offers strong prognostic insights for HNSCCs, guiding precise diagnosis, treatment, and assisting in clinical decision-making.

Banxia Xiexin Decoction Prevents HT22 Cells From High Glucose-Induced Neurotoxicity via JNK/SIRT1/Foxo3a Signaling Pathway.

BACKGROUND: Type 2 diabetes-associated cognitive dysfunction (DCD) is a chronic complication of diabetes that has gained international attention. The medicinal compound Banxia Xiexin Decoction (BXXXD) from traditional Chinese medicine (TCM) has shown potential in improving insulin resistance, regulating endoplasmic reticulum stress (ERS), and inhibiting cell apoptosis through various pathways. However, the specific mechanism of action and medical value of BXXXD remain unclear. METHODS: We utilized TCMSP databases to screen the chemical constituents of BXXXD and identified DCD disease targets through relevant databases. By using Stitch and String databases, we imported the data into Cytoscape 3.8.0 software to construct a protein-protein interaction (PPI) network and subsequently identified core targets through network topology analysis. The core targets were subjected to Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The results were further validated through in vitro experiments. RESULTS: Network pharmacology analysis revealed the screening of 1490 DCD-related targets and 190 agents present in BXXXD. The topological analysis and enrichment analysis conducted using Cytoscape software identified 34 core targets. Additionally, GO and KEGG pathway analyses yielded 104 biological targets and 97 pathways, respectively. BXXXD exhibited its potential in treating DCD by controlling synaptic plasticity and conduction, suppressing apoptosis, reducing inflammation, and acting as an antioxidant. In a high glucose (HG) environment, the expression of JNK, Foxo3a, SIRT1, ATG7, Lamp2, and LC3 was downregulated. BXXXD intervention on HT22 cells potentially involved inhibiting excessive oxidative stress, promoting neuronal autophagy, and increasing the expression levels of JNK, SIRT1, Foxo3a, ATG7, Lamp2, and LC3. Furthermore, the neuroprotective effect of BXXXD was partially blocked by SP600125, while quercetin enhanced the favorable role of BXXXD in the HG environment. CONCLUSION: BXXXD exerts its effects on DCD through multiple components, targets, levels, and pathways. It modulates the JNK/SIRT1/Foxo3a signaling pathway to mitigate autophagy inhibition and apoptotic damage in HT22 cells induced by HG. These findings provide valuable perspectives and concepts for future clinical trials and fundamental research.

Exploration of molecular mechanism underlying protective effect of astragaloside IV against radiation-induced lung injury by suppressing ferroptosis.

In this study, we aimed to investigate the pharmacological effects and underlying mechanisms of astragaloside IV (AS IV) against radiation-induced lung injury. We established experimental models of radiation-induced lung injury and observed the effect of AS IV on cell viability, cell death, inflammatory responses and ferroptosis. Accordingly, we found that AS IV restored the suppressed cell viability and promoted cell death induced by X-ray irradiation. Moreover, radiation-induced up-regulation of lactate dehydrogenase (LDH) release, ferroptosis, reactive oxygen species (ROS) and inflammatory responses were also restored by AS IV in a dose-dependent manner. Besides, in radiation-induced lung injury C57BL/6 mice, AS IV evidently alleviated lung injury and promoted the survival rate of lung-injured mice. And the ferroptosis level in mice lung tissues were also alleviated by the administration of AS IV in a dose-dependent manner. As a conclusion, by comparing the changes of ferroptosis, ROS and inflammatory responses in the experimental models, we validated that AS IV could inhibit inflammatory responses and cell injury in the treatment of radiation-induced lung injury by suppressing ferroptosis. This finding not only find potentially effective treatments to mitigate radiation-induced lung injury, but also provides supporting evidence for clinical application of AS IV to improve the management of radiation-treated patients and minimize the associated lung complications or other adverse effects. Moreover, as inflammation and ROS are key contributors to tissue damage in various diseases, our study suggested the potential application of AS IV in the treatments for other diseases.

Overview of research progress and application of experimental models of colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancy in terms of global tumor incidence, and the rates of morbidity and mortality due to CRC are rising. Experimental models of CRC play a vital role in CRC research. Clinical studies aimed at investigating the evolution and mechanism underlying the formation of CRC are based on cellular and animal models with broad applications. The present review classifies the different experimental models used in CRC research, and describes the characteristics and limitations of these models by comparing the research models with the clinical symptoms. The review also discusses the future prospects of developing new experimental models of CRC.

Cuproptosis-related lncRNAs predict prognosis and immune response of thyroid carcinoma.

Objective: To estimate the survival and prognosis of patients with thyroid carcinoma (THCA) based on the Long non-coding RNA (lncRNA) traits linked to cuproptosis and to investigate the connection between the immunological spectrum of THCA and medication sensitivity. Methods: RNA-Seq data and clinical information for THCA were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We built a risk prognosis model by identifying and excluding lncRNAs associated with cuproptosis using Cox regression and LASSO methods. Both possible biological and immune infiltration functions were investigated using Principal Component Analysis (PCA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and immunoassays. The sensitivity of the immune response to possible THCA medicines was assessed using ratings for tumor immune dysfunction and exclusion (TIDE) and tumor mutational burden (TMB). Results: Seven cuproptosis-related lncRNAs were used to construct our prognostic prediction model: AC108704.1, DIO3OS, AL157388.1, AL138767.3, STARD13-AS, AC008532.1, and PLBD1-AS1. Using data from TCGA's training, testing, and all groups, Kaplan-Meier and ROC curves demonstrated this feature's adequate predictive validity. Different clinical characteristics have varying effects on cuproptosis-related lncRNA risk models. Further analysis of immune cell infiltration and single sample Gene Set Enrichment Analysis (ssGSEA) supported the possibility that cuproptosis-associated lncRNAs and THCA tumor immunity were closely connected. Significantly, individuals with THCA showed a considerable decline in survival owing to the superposition effect of patients in the high-risk category and high TMB. Additionally, the low-risk group had a higher TIDE score compared with the high-risk group, indicating that these patients had suboptimal immune checkpoint blocking responses. To ensure the accuracy and reliability of our results, we further verified them using several GEO databases. Conclusion: The clinical and risk aspects of cuproptosis-related lncRNAs may aid in determining the prognosis of patients with THCA and improving therapeutic choices.

A Network Pharmacology Approach for Uncovering the Mechanism of 'Kouchuangling' in Radiation-induced Oral Mucositis Treatment.

BACKGROUND: Radiation-induced oral mucositis (RIOM) is an intractable inflammatory disease whose pathogenesis needs to be clarified. "Kouchuangling" (KCL), a traditional Chinese medicine formula, is composed of Lonicerae Japonicae Flos, Radix Paeoniae Rubra, and Radix Sanguisorbae. Although all of them are Chinese folk medicines which have long been utilized for ameliorating inflammation, the mechanism of KCL to RIOM remains unclear. PURPOSE: To predict the active ingredients of KCL and identify the mechanism of KCL on RIOM. MATERIALS AND METHODS: We identified the chemical ingredients in KCL using TCM Systems Pharmacology (TCMSP), TCM@Taiwan, PubChem, and SuperPred databases and used the oral bioavailability (OB), drug-like properties (DL) and Degree of compounds for screening. Targets for oral mucositis were obtained from the Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), PharmGKB, and DrugBank databases. Cytoscape 3.7.0 was used to visualize the compound-target-disease network for KCL and RIOM. The biological processes of target gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using DAVID. RESULTS: Based on OB≥30%, DL≥0.18 and Degree≥3, 24 active ingredients and 960 targets on which the active components acted were identified. A total of 1387 targets for oral mucositis were screened. GO enrichment and KEGG pathway analyses resulted in 43 biological processes (BPs), 3 cell components (CCs), 5 molecular functions (MFs), and 32 KEGG pathways, including leishmaniasis, Toll-like receptor signaling, TNF signaling, and Influenza A pathways. CONCLUSION: This experiment preliminarily verified that the active ingredients of KCL play a role in the treatment of RIOM through multiple targets and pathways, providing a reference for further study of the pharmacological mechanism of Chinese herbal medicine.

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury.

Myocardial ischemia and reperfusion injury (MIRI), induced by coronary heart disease (CHD), causes damage to the cardiomyocytes. Furthermore, evidence suggests that thrombolytic therapy or primary percutaneous coronary intervention (PPCI) does not prevent reperfusion injury. There is still no ideal animal model for MIRI. This study aims to improve the MIRI model in rats to make surgery easier and more feasible. A unique method for establishing MIRI is developed by using a soft tube during a key step of the ischemic period. To explore this method, thirty rats were randomly divided into three groups: sham group (n = 10); experimental model group (n = 10); and existing model group (n = 10). Findings of triphenyltetrazolium chloride staining, electrocardiography, and percent survival are compared to determine the accuracies and survival rates of the operations. Based on the study results, it has been concluded that the improved surgery method is associated with a higher survival rate, elevated ST-T segment, and larger infarct size, which is expected to mimic the pathology of MIRI better.

DNAH7 mutations benefit colorectal cancer patients receiving immune checkpoint inhibitors.

Background: Colorectal cancer (CRC) is a malignant tumor associated with a high mortality rate. While the advent of immune checkpoint inhibitors (ICIs) has been a gamechanger, only a small percentage of CRC patients benefit from ICIs. The pathological mechanism of CRC is not well understood, but somatic mutations, especially missense mutations, are believed to play an important role. This study examined the relationship between ICIs in colorectal cancer and missense mutations in the axonemal dynein heavy chain gene 7 (DNAH7). Methods: A clinical cohort (n=690) and the CRC data from the publicly available Cancer Genome Atlas (TCGA) were examined. Gene Set Enrichment Analysis, ESTIMATE analysis, and clinical correlation analysis were performed to explore the effects and mechanisms of DNAH7 mutation on immunotherapy in colorectal cancer. Results: The results showed that CRC patients with DNAH7 mutations can benefit more from ICIs (P<0.05). Patients with DNAH7 mutation had higher ESTIMATE scores, immune scores, and matrix scores, compared to patients without the DNAH7 mutation (P<0.001). The transport of small molecules, keratinization, asthma, autoimmune thyroid disease, allograft rejection, and other pathways were significantly enriched in DNAH7 mutated tissues (P<0.05). The top key genes associated with the DNAH7 mutation included AQP8, MS4A12, GUCA2B, and ZG16 (P<0.01). Conclusions: The current study not only demonstrated the significance of DNAH7 as a risk factor and prognostic feature in CRC, but also revealed that DNAH7 mutations might affect the clinical efficacy of ICIs by impacting the tumor immune microenvironment.

Celastrol induces caspase-dependent apoptosis of hepatocellular carcinoma cells by suppression of mammalian target of rapamycin.

OBJECTIVE: To investigate the efficacy of celastrol treatment of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to propose a mechanism of action. METHODS: A human HepG2 liver cancer cell line and a xenograft tumor model were used to investigate the effects of celastrol on HCC in vitro and in vivo. A CCK-8 kit was used to detect cell viability. Flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining were used to detect apoptosis. Western blotting and immunohistochemistry were used to detect the expression of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, mammalian target of rapamycin (mTOR), and p-mTOR. Hematoxylin-eosin staining was used to observe the tissue morphology. RESULTS: Celastrol decreased the viability of HepG2 cells and induced apoptosis. Western blot assays indicated that celastrol up-regulated cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, and cleaved-PARP by inhibiting the phosphorylation of mTOR in HepG2 cells. Moreover, celastrol inhibited the tumor growth in a xenograft model. Celastrol also induced caspase-dependent apoptosis (up-regulation of cleaved-caspase- 3, -8, -9, and cleaved-PARP) and inhibited the activation of mTOR in vivo. CONCLUSION: Celastrol induces caspase-dependent apoptosis in HCC cells by inhibiting the activation of mTOR.

Maimendong and Qianjinweijing Tang (Jin formula) suppresses lung cancer by regulation of miR-149-3p.

ETHNOPHARMACOLOGICAL RELEVANCE: Maimendong and Qianjinweijing Tang (Jin formula), a classic Chinese formula, can enhance therapeutic efficacy and reduce adverse effects in patients with lung cancer. AIM OF THE STUDY: To evaluate the anti-lung cancer effect of Jin formula in vivo and in vitro, and to explore the role of microRNA (miRNA) in the anti-lung cancer mechanism of Jin formula. MATERIALS AND METHODS: Cell survival was determined via a colorimetric method, and apoptotic condition was revealed by flow cytometric analysis. Cell migration and invasion were detected by scratch and transwell assays. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was applied to measure the changes of miRNA expression. Pathological histology of lung tissues were assessed by hematoxylin-eosin (HE) staining. Immunohistochemistry and immunoblotting were used to detect the expression of marker proteins of Wnt/ß-catenin pathway. The relationship between miR-149-3p and MYC associated zinc finger protein (MAZ) was verified using a dual-luciferase reporter assay system. RESULTS: Our findings demonstrated the anti-cancer effect of Jin formula in vitro, and revealed that Jin formula could suppress the proliferation, migration and invasion of human lung cancer A549 and H1299 cells. We also confirmed the capability of Jin formula to reduce tumor growth through the up-regulation of miR-149-3p and down-regulation of Wnt/ß-catenin signaling in animal models. qRT-PCR analysis in vitro further confirmed a dose-dependent increase of miR-149-3p by treatment with Jin formula. Functional studies identified MAZ as a downstream target of miR-149-3p. Overexpression of miR-149-3p inhibited cell proliferation, migration, invasion and induced apoptosis in A549 and H1299 cells, similar to our findings on the effects of Jin formula treatment. In contrast, inhibiting the expression of miR-149-3p reversed the anti-cancer effects of Jin formula. Additionally, we revealed that miR-149-3p was involved in the anti-cancer effects of Jin formula, at least in part, by inhibiting MAZ expression and the Wnt/ß-catenin signaling cascade. CONCLUSION: Our study illustrated that Jin formula suppressed the development of lung cancer and the mechanism may be associated with the miR-149-3p/MAZ/Wnt/ß-catenin axis.

Xiaoai Jiedu Recipe Inhibits Proliferation and Metastasis of Non-Small Cell Lung Cancer Cells by Blocking the P38 Mitogen-Activated Protein Kinase (MAPK) Pathway.

BACKGROUND Lung cancer is the leading cause of cancer deaths in the world. Its major histopathological subtype is non-small cell lung cancer (NSCLC). Xiaoai Jiedu recipe (XJR) is a traditional Chinese medicine formula that can suppress growth and invasion of tumor cells. Here, we assessed the antitumor effect of XJR on NSCLC explored the underlying mechanisms. MATERIAL AND METHODS Three concentrations of XJR (low, middle, and high) were used to treat A549 cells. Cell Counting Kit-8 and colony formation assay were used to measure proliferation of A549 cells. Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry. The expression of apoptosis-associated proteins was measured by Western blot analysis. Transwell and scratch wound healing assay were used to assess invasion and migration, respectively, of A549 cells. The expression of p38 MAPK pathway-associated proteins were measured using Western blot analysis. RESULTS XJR suppressed proliferation and promoted apoptosis of A549 cells, especially in the high-dose group. The expression of Bcl-2 was reduced with increasing expression of Bax, cleaved caspase-3, and cleaved caspase-9. Invasion and migration abilities of A549 cells were inhibited after XJR treatment. XJR treatment decreased the expression levels of phosphorylated p38 (p-p38), p-ERK, and p-JNK in a dose-dependent manner. CONCLUSIONS The results demonstrated that XJR can inhibit proliferation, invasion, and migration, and induce apoptosis of NSCLC by blocking the p38 MAPK pathway, which shows the potential of XJR as a new treatment of NSCLC.

Identification of key pathways and genes in colorectal cancer to predict the prognosis based on mRNA interaction network.

The aim of the present study was to identify key genes in colorectal cancer (CRC) that could be used to reliably diagnose this disease and to explore the potential underlying mechanisms in silico. The gene expression profiles of primary human cancer datasets GSE21510 and GSE32323 were downloaded from the Gene Expression Omnibus database. The limma R software package was used to identify differentially expressed (DE) genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on DE genes using the Database for Annotation, Visualization and Integrated Discovery. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to construct a protein-protein interaction (PPI) network of the DE genes. Survival rate was analyzed and visualized using The Cancer Genome Atlas (TCGA). A total of 1,126 genes were significantly DE in the present study. All DE genes were enriched in KEGG pathways including 'cell cycle', 'mineral absorption', 'pancreatic secretion', 'pathways in cancer', 'metabolic pathways', 'aldosterone-regulated sodium reabsorption' and 'Wnt signaling pathway'. A total of 5 hub genes enriched in cell cycle and tumor-associated pathways, including E2F2, SKP2, MYC, CDKN1A and CDKN2B, were significantly DE and validated between tumor and normal tissues. CDKN1A and CDKN2B were identified within the PPI network using the Molecular Complex Detection algorithm. Survival and content distribution analyses of 362 clinical samples from TCGA revealed that CDKN1A effectively predicted the prognosis of patients. The present study identified key genes and potential signaling pathways involved in CRC. These findings may provide new insights for survival assessment during the clinical diagnosis of CRC.

Quercetin inhibits growth of hepatocellular carcinoma by apoptosis induction in part via autophagy stimulation in mice.

Quercetin (QCT) has been shown to have anticancer activities associated with apoptosis and autophagy induction. However, whether autophagy is functionally responsible for the inhibitory effect of QCT on hepatocellular carcinoma (HCC) remains elusive. This study aims to investigate if QCT inhibits HCC growth via autophagy induction. The in vitro experiments showed that QCT inhibited the growth of human HCC cells in dose- and time-dependent manners and had minimal cytotoxicity to normal hepatocytes. QCT increased both autophagosomes and autolysosomes in HCC cells, as determined by electron microscopy, GFP-RFP-LC3 fluorescence confocal microscopy and Western blot analysis of autophagy-related biomarkers. Functional assays using pathway-specific inhibitors, activators or siRNAs indicated that QCT stimulated autophagy in part via inhibiting the AKT/mTOR pathway and activating the MAPK pathways. Further functional experiments using autophagy inhibitors demonstrated that QCT induced apoptosis of HCC cells in part via stimulating autophagy. The in vivo studies showed that QCT significantly inhibited tumor growth associated with apoptosis induction and autophagy stimulation, and that inhibition of autophagy significantly alleviated the QCT effect on tumor growth inhibition and apoptosis induction. To the best of our knowledge, this is the first in vivo report to demonstrate that QCT inhibits HCC tumor growth and induces apoptosis in part via stimulation of autophagy. Our results provide strong experimental evidence to support that autophagy stimulation may be an important mechanism by which QCT induces cancer cell apoptosis, and pave the way for further clinical investigations by applying QCT or QCT-rich foods for HCC intervention.

6-Gingerol inhibits proliferation in gastric cancer via the STAT3 pathway in vitro.

With high incidence and mortality, gastric cancer seriously threatened human's life. It is arduous and necessary to investigate its pathogenesis and dig effective drugs. In this study, we explored the role of 6-Gingerol (GI), a natural active ingredient, in treating gastric cancer cells. MTT assay and colony formation assay were utilized to confirmed that GI can control the proliferation of gastric cancer cells, which is time and concentration-dependent to some extent. The Annexin V-FITC/PI staining results by flow cytometry reveal that GI induces the apoptosis of gastric cancer cells. And a study on further pathways by western blot shows that GI brings about cell apoptosis by inhibiting the activation of STAT3. GI therefore may be a good candidate for treating gastric cancer.

2-Hydroxy-3-methylanthraquinone inhibits lung carcinoma cells through modulation of IL-6-induced JAK2/STAT3 pathway.

BACKGROUND: 2-hydroxy-3-methylanthraquinone (HMA), an anthraquinone monomer in traditional Chinese medicine Hedyotis diffusa, has been reported to inhibit the growth of several types of cancer, but its effect on lung cancer has not been adequately investigated. HYPOTHESIS/PURPOSE: This study aimed to test the hypothesis that HMA inhibit the growth, migration, and invasion of lung cancer cells in part via downregulation of interleukin (IL)-6-induced JAK2/STAT3 pathway. METHODS: Growth and apoptosis of lung cancer cells were quantitated by CCK-8 assay and Annexin V-FITC/PI flow cytometric analysis, respectively. Migration and invasion of A549 cells were determined by wound-healing assay and transwell invasion assay, respectively. The effect of HMA on cytokines expression in A549 cells was evaluated by the cytokine antibody array assay. Gene expression and protein levels of related molecular markers were quantitated by real time-PCR and Western blot analysis, respectively. RESULTS: HMA significantly inhibited IL-6-stimulated growth and colony formation of A549 cells, increased the number of apoptotic cells, and inhibited invasion associated with downregulation of expression of IL-6-induced MMP-1, MMP-2, and MMP-9 genes. IL-6 increased the levels of tyrosine phosphorylation of JAK2 and STAT3 in A549 cells, which was reversed by HMA treatment. In addition, HMA reduced the expression of a series of inflammation-related cytokines in A549 cells supernatant, including IL-6, G-CSF, IL-6R, IL-8, MCP-1, RANTES, TNF-α. CONCLUSION: These results suggest that HMA may inhibit the growth and invasion of lung cancer cells in part via downregulation of IL-6-induced JAK2/STAT3 pathway.

Demethylzeylasteral (T-96) inhibits triple-negative breast cancer invasion by blocking the canonical and non-canonical TGF-ß signaling pathways.

Inflammation is one of the characteristic features during the development of human tumors. A pro-inflammatory cytokine that is known to promote inflammation during cancer development is the transforming growth factor-ß (TGF-ß). On the other hand, demethylzeylasteral (T-96) is a natural compound isolated from Tripterygium wilfordii Hook F, which has been reported to have various pharmacological properties including anti-inflammatory and immunosuppressive activities. We investigated the effects of T-96 on the highly metastatic breast cancer cell line, MDA-MB-231. Cell migration was assessed by scratch-wound migration assay, and the molecular mechanisms underlying the effects of T-96 were examined by qPCR and Western blot analyses. We also investigated the suppression effects of T-96 on the pulmonary metastasis in the 4T1 mouse model. T-96 inhibited TGF-ß-induced migration and epithelial-mesenchymal transition both in vitro and in vivo. These results demonstrate that T-96 inhibited invasion of MDA-MB-231 and 4T1 cells via suppressing the canonical and non-canonical TGF-ß signaling pathways.

Retraction: Cyclooxygenase-2 mediates puerarin to inhibit the invasion and metastasis of lung cancer A549 cells.

[This retracts the article DOI: 10.21037/tcr.2017.06.18.].