Based on LC-MS technology explored the metabolomics of Agrimonia pilosa intervening in non-small cell lung cancer A549 cells / 药学学报

The objective of this study was to analyze the effects on cell viability, apoptosis, and cell cycle of non-small cell lung cancer (NSCLC) A549 cells after intervention with Agrimonia pilosa (AP) and investigate Agrimonia pilosa anti-tumor activity in vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) metabolomics technology was used to analyze the changes of cellular metabolites and metabolic pathways. The results of this study will provide a theoretical and experimental basis for investigating the mechanism of the effect of Agrimonia pilosa on non-small cell lung cancer A549 cells. The results showed that the cell nucleus of A549 cells crumpled and apoptosis occurred with the increase of drug concentration. The survival rate of the cells decreased, and the inhibition rate reached 21.5% and 91.74% under the low and high dose conditions, respectively. Lactate dehydrogenase (LDH) content increased (P < 0.05). Metabolomics results showed significant differences in metabolism between groups, thirty-three distinct metabolites including LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) were deduced. The pathway enrichment showed that the Agrimonia pilosa plays an anti-tumor role mainly by regulating the metabolism of glycerophosphate and purine in A549 cells, in which the effect on glycerophosphate metabolism pathway was most significant. The results of combined pharmacodynamics suggested that Agrimonia pilosa might induce apoptosis and inhibit the growth of A549 cells by regulating LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) metabolites in A549 cells.

Establishment and biological characterization of drug-resistant cells and identification of multidrug resistance in small-cell lung cancer / 中国药理学通报

Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q

Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways / 中国药理学通报

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

A network pharmacology-based approach to explore mechanism of kaempferol-7 -O -neohesperidoside against prostate cancer / 中国药理学通报

Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.

Curcumin Induces Cycle Arrest of Colon Cancer HCT116 Cells via JAK1/STAT1/p21 Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of curcumin on the cycle arrest of human colon cancer HCT116 cells and decipher the possible molecular mechanism. MethodThe methyl thiazolyl tetrazolium （MTT） method was employed to examine the effects of curcumin （0， 12.5， 25， 50， 75， 100 μmol·L-1） and 5-fluorouracil （5-FU， 600 μmol·L-1） on the proliferation of HCT116 cells at different time points （24， 48， 72 h）. Flow cytometry was employed to examine the cycle of HCT116 cells treated with curcumin （0， 25， 50， 75 μmol·L-1） and 5-FU. Western blot was employed to determine the expression of proteins in the Janus kinase 1 （JAK1）/signal transducer and activator of transcription 1 （STAT1） /cyclin-dependent kinase inhibitor 1A （p21） pathway in HCT116 cells. The binding of STAT1 to p21 promoter region was detected by chromatin immunoprecipitation （ChIP）. Small interfering RNA （siRNA） was employed to measure the role of STAT1 in regulating the expression of p21 and that of JAK1 in regulating the activation of STAT1 by Western blot and cellular immunofluorescence， respectively. ResultCompared with the blank group， the HCT-116 cells treated with curcumin and 5-FU showed decreased viability （P<0.05）， increased proportions of cells in the G0/G1 phase （P<0.05）， decreased proportions of cells in the S phase and G2/M phase （P<0.05）， down-regulated protein level of phosphorylated p21 （P<0.05）， and up-regulated protein level of p21 （P<0.05）. Compared with the curcumin group， the p21 siRNA+ curcumin group presented decreased proportion of cells in G0/G1 phase （P<0.05）. Compared with the blank group， curcumin elevated the level of phosphorylated STAT1 （p-STAT1） （P<0.05）. Compared with the curcumin group， the curcumin + STAT1 siRNA group showcased up-regulated protein level of p21 in HCT116 cells （P<0.05）. The mechanism study showed that curcumin treatment enhanced the enrichment of STAT1 in the p21 promoter region （P<0.05） compared with the blank group. Compared with the blank group， curcumin up-regulated the level of phosphorylated JAK1 （p-JAK1） （P <0.05）. Compared with the curcumin group， the curcumin + STAT1 siRNA group demonstrated up-regulated protein levels of p-STAT1 and p21 in HCT116 cells （P<0.05）. ConclusionCurcumin may induce the cycle arrest of human colon cancer HCT116 cells by activating the JAK1/STAT1/p21 signaling pathway.

Effects of occupational radiation exposure on peripheral blood lymphocyte count and cell cycle in logging workers / 中国辐射卫生

Objective To investigate the effects of prolonged low-dose neutron-γ radiation on peripheral blood lymphocytes of logging workers. Methods The health information of workers in a logging company was collected by on-site blood sample collection and questionnaire survey. Individual doses of γ and neutron radiation were recorded using LiF elements and CR-39, respectively. Lymphocyte count in peripheral blood was measured by blood cytometer. Cell cycle and cyclins were detected by flow cytometry. Results The annual dose of some logging workers exceeded 5 mSv. Lymphocyte counts showed a difference of 15% between the group exposed to the lowest annual dose of 0–1 mSv (mean: 2.45 × 109/L) and the group exposed to the highest annual dose of 5–25 mSv (mean: 2.08 × 109/L). In comparison to pre-shift workers, logging workers exhibited a G1-phase arrest in the lymphocyte cycle, along with increased expression of cyclins p21 and CDK2. Conclusion Prolonged exposure to low-dose neutron-γ radiation leads to reduced lymphocyte counts as well as changes in lymphocyte cycle and cyclin expression.

Mechanism of Qizhu Kang'ai Prescription for Inhibiting Proliferation of Hepatocellular Carcinoma by Regulating Tumor Metabolic Reprogramming via PCK1/Akt/p21 Signal Axis / 中国实验方剂学杂志

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl4） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl4 was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G0/G1 phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G0/G1 phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G0/G1 phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Identification and Analysis of SND1 as an Oncogene and Prognostic Biomarker for Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Transcription factor (TF) can bind specific sequences that either promotes or represses the transcription of target genes, and exerts important effects on tumorigenesis, migration, invasion. Staphylococcal nuclease-containing structural domain 1 (SND1), which is a transcriptional co-activator, is considered as a promising target for tumor therapy. However, its role in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore the role of SND1 in LUAD.@*METHODS@#Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) database was obtained to explore the association between SND1 and the prognosis, as well as the immune cell infiltration, and subcellular localization in LUAD tissues. Furthermore, the functional role of SND1 in LUAD was verified in vitro. EdU assay, CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot were performed.@*RESULTS@#SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1.@*CONCLUSIONS@#SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma

Background Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood. Results miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models. Conclusions These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.

Síntesis y actividad antiproliferativa de una mezcla de derivados de (+/_) 7-clo-ro-(4-tioalquilquinolina). Inducción de apoptosis y daño sobre el ADn/aRN

Después de las enfermedades cardiovasculares, el cáncer, una patología no transmisible, ha sido considerado como la segunda causa de muertes cada año a nivel global y como la barrera más importante para aumentar la esperanza de vida en el siglo 21. Se han alcanzado avances de gran relevancia en su prevención y tratamiento; sin embargo, existe aún un largo camino por recorrer para alcanzar un tratamiento efectivo para cada tipo de cáncer. En este trabajo se describen enfoques de reposicionamiento y síntesis de moléculas híbridas con potencial actividad antineoplásica. Para obtener el al-dehído intermediario clave, se empleó la metodología de oxidación de Dess-Martin, que fue acoplado con las cetonas correspondientes usando LDA; se generó así una mezcla racémica para cada uno de los compuestos híbridos propuestos. La actividad antiproliferativa in vitro de los compuestos finales se evaluó frente a ocho líneas celulares derivadas de tumores sólidos humanos, y cuatro líneas celulares no cancerosas. El compuesto 11d resulto ser el más efectivo y con mayor índice de seguridad. Los resultados sugirieron que estos compuestos podrían bloquear el ciclo celular e inducir la apop-tosis y la muerte en las células CCRF-CEM de forma dependiente de la dosis in vitro.

After cardiovascular diseases, cancer, a non-communicable pathology, has been considered the second cause of death each year globally and as the most important barrier to increasing life expectancy in the 21st century. Advances of great relevance have been made in its prevention and treatment, however, there is still a long way to go to achieve an effective treatment for each type of cancer. This paper describes approaches to reposition and synthesis of hybrid molecules with potential antineoplastic activity. To obtain the key intermediate aldehyde, the Dess-Martin oxidation methodology was used, which was coupled with the corresponding ketones using LDA. The final hybrid compounds were obtained as a racemic mixture. The in vitro antiproli-ferative activity of the final compounds was evaluated against eight cell lines derived from human solid tumors, and four non-cancerous cell lines. The compound 11d turned out to be the most effective and with the highest safety index. The results suggested that these compounds could block the cell cycle and induce apoptosis and death in CCRF-CEM cells in a dose-dependent manner in vitro.

Depois das doenças cardiovasculares, o câncer, uma patologia não transmissível, tem sido considerado como a segunda causa de mortes a cada ano em todo o mundo e como a barreira mais importante para o aumento da expectativa de vida no século 21. Avanços de grande relevância têm sido feitos na sua prevenção e tratamento, no entanto, ainda há um longo caminho a percorrer para alcançar um tratamento eficaz para cada tipo de câncer. Este artigo descreve abordagens para o reposicionamento e síntese de moléculas híbridas com potencial atividade antineoplásica. Para a obtenção do aldeído intermediário chave, foi utilizada a metodologia de oxidação de Dess-Martin, que foi acoplada com as cetonas correspondentes usando LDA. Os compostos híbridos finais foram obtidos como uma mistura racêmica. A atividade antiproliferativa in vitro dos compostos finais foi avaliada contra oito linhagens celulares derivadas de tumores sólidos humanos e quatro linhagens celulares não cancerosas. O composto 11d revelou-se o mais eficaz e com o maior índice de segurança. Os resultados sugeriram que estes compostos poderiam bloquear o ciclo celular e induzir apoptose e morte em células CCRF-CEM de forma dose-de-pendente in vitro.

Hippo-YAP pathway is involved in the effect of NaAsO / 中国药理学通报

Aim To explore the effects of NaAsO

Effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression and its mechanism / 中国药理学通报

Aim To investigate the effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression in nude mice bearing colorectal cancer. Methods Male BALB/C nude mice were inoculated with human colon cancer cell HT-29 under the armpit. The tumor bearing nude mice were randomly divided into five groups: control group, chemotherapy group, positive drug group, Lulong Zaisheng Decoction II groups with high and low doses. The mice were given drugs by gavage once a day for 10 consecutive days. From the fourth day of the experiment, except for the control group, the nude mice were intraperitoneally injected with 5-FU at dose of 25 mg • kg

Artesunate inhibits development of esophageal squamous cell carcinoma via regulating expression of Skp2 and P21 / 中国药理学通报

Aim To clarify the regulatory effect of Artesunate(ART) on tumor cell function and cell cycle in the pathological process of esophageal squamous cell carcinoma(ESCC). Methods KYSE450 and TE14 cells were treated with different concentrations of ART. The cells treated with 0 mg •L

Sensitizing effect of d-borneol on cisplatin-resistant NSCLC based on transcriptomics and its mechanism / 中国药理学通报

Aim To explore the key targets of d-borneol combined with eisplatin for sensitization of cisplatin-resistant NCSLC cells by RNA-Seq and verify its mechanism. Methods Cisplatin-resistant human large cell lung cancer cells (H460/CDDP) were inoculated into the right armpit of male BALB/c nude mice (4 weeks old) to construct a xenograft tumor model. Then they were randomly divided into control group, vehicle group, eisplatin group, and combination group (d-borneol + eisplatin) with 6 nude mice and treated for 14 d. After last administration of 24 h, the tumor tissue was taken for RNA-Seq. And then real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to verify the expression of cell cycle-related molecules. Results RNA-seq analysis showed that there were significant differences in gene expression between the eisplatin group and combined group, and they were significantly enriched in cell cycle. RT-PCR and IHC results showed that d-borneol combined with eisplatin could significantly inhibit the expressions of cyclins (cyclin A2, cyclin D3) and cyclin-dependent kinases (CDK2, CDK6) and promote the expression of its upstream molecular cyclin-dependent kinase inhibitor CD-KI (P21, P27) (P<0. 05, P<0.01). Conclusions d-Borneol increases the sensitivity of eisplatin by increasing the expression of P21 and P27 and inhibiting the expression of cyclinA2/D3 and CDK2/6 to induce cell cycle arrest and inhibit the malignant proliferation of H460/CDDP cells, thereby achieving the effect of anti-drug sensitization.

Role of epigenetic regulation of biological clock genes in tumors / 中国药理学通报

The circadian clock is regulated at the molecular level by transcriptional-translational feedback loop of clock genes, which ensures that a variety of physiological processes have a-round 24 h circadian rhythms, including cell metabolism, cell proliferation, cell apoptosis and tumorigenesis, to maintain the homeostasis. Thus, the disturbance of circadian clock will disrupt homeostasis, causing various diseases, including neoplasm, metabolic syndrome, Parkinson's disease, COPD and cardiovascular diseases. Disturbance of circadian clock is closely related with tumorigenesis, and acts on various molecules and pathways leading to tumorigenesis, including oncogene and tumor suppressor gene, cell cycle, metabolic reprogramming, immune escape, endocrine disruption, alteration of gastrointestinal microbiome. This review focuses on changes in clock genes expression which disrupt cell cycle and may play a role in tumorigenesis, and epi-geneties, an important way to regulate gene expression, which can alter clock gene expression, thus playing an important role in the process of " the alternation of clock gene expression-disruption of cell cycle-tumorigenesis".

Artesunate inhibits development of breast cancer cells via affecting expression of Skp2 and CDKN1A / 中国药理学通报

Aim To explore the effect of artesunate (ART) on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action. Methods MCF-7 (30 μmol • L-

Effects and related mechanisms of histone deacetylase inhibitors on the proliferation of choroidal melanoma C918 cell line / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To elucidate the effect of histone deacetylase(HDAC)inhibitor suberoylanilide hydroxamic acid(SAHA)on the proliferation of choroidal melanoma(CM)cell line C918 and to explore the related mechanism.METHODS: Inverted fluorescence microscope was used to observe the effect of different concentrations of SAHA(0.625, 1.25 or 2.5 μmol/L)on the morphology of C918 cell. The cell viability was detected by cholecystokinin octapeptide(CCK-8)assay. Plate clone formation assay and EdU staining were carried out to measure the effect of SAHA on the cell proliferation. Meanwhile, the expressions of cell proliferation-related proteins including c-Myc, CyclinA2 and CDK2, and histone deacetylase 7(HDAC7)and fibroblast growth factor 18(FGF18)were detected by Western blot.RESULTS: Compared with the control group, the cell density was reduced in SAHA. SAHA could also promote cell shrinkage, and the inhibition on cell was in a concentration-dependent manner. CCK-8 assay showed that SAHA treatment decreased cell viability in a dose-dependent manner and the inhibition rate was 80% when SAHA at 2.5 μmol/L. Compared with the control group, Western blot showed that SAHA could suppress the expression of cell proliferation proteins including c-Myc, CyclinA2 and CDK2 in a dose-dependent manner. In addition, 1.25 μmol/L SAHA significantly decreased the numbers of EdU staining positive cells and cell clones. More importantly, SAHA could dose-dependently decrease the expression of HDAC7 and FGF18 compared with control group.CONCLUSION: SAHA could inhibit the proliferation of CM cell line C918 by inhibiting the HDAC7/FGF18 signaling pathway.

Maackiain inhibits proliferation and promotes apoptosis of nasopharyngeal carcinoma cells by inhibiting the MAPK/Ras signaling pathway / 中国天然药物

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.

Nano-ayurvedic medicine and its potential in cancer treatment / 中西医结合学报

Nano-ayurvedic medicine is an emerging field in which nanoparticles are functionalized with active principles of potent ayurvedic herbs to enhance their efficacy and target-specific delivery. Scientific advances in the past couple of decades have revealed the molecular mechanisms behind the anticancer potential of several ayurvedic herbs, attributed chiefly to their secondary metabolites including polyphenols and other active substances. With the advancement of nanotechnology, it has been established that size-, shape-, and surface-chemistry-optimized nanoparticles can be utilized as synergizing carriers for these phytochemicals. Nano-ayurvedic medicine utilizes herbs that are commonly used in Ayurveda to functionalize different nanoparticles and thereby enhance their potency and target specificity. Studies have shown that the active phytochemicals of such herbs can be coated onto the nanoparticles of different metals, such as gold, and that they work more efficiently than the free herbal extract, for example, in inhibiting cancer cell proliferation. Recently, an Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homeopathy (AYUSH)-based clinical trial in humans indicated the anticancer potential of such formulations. Nano-ayurvedic medicine is emerging as a potential treatment option for hyperproliferative diseases.

Licochalcone A induces cell cycle arrest in human lung squamous carcinoma cells via the PI3K/Akt signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of licochalcone A (LCA) on the proliferation and cell cycle of human lung squamous carcinoma cells and explore its possible molecular mechanism.@*METHODS@#MTT assay was used to detect the changes in proliferation of H226 cells after treatment with different concentrations of LCA for 48 h, and the IC50 of LCA was calculated. Flow cytometry was used to analyze cell cycle changes in H226 cells treated with 10, 20, and 40 μmol/L LCA, and the expressions of cyclin D1, cyclin-dependent kinase CDK2 and CDK4, and p-PI3K, PI3K, p-Akt, and Akt in the treated cells were detected using Western blotting. The effect of intraperitoneal injection of LCA for 24 days on tumor volume and weight was assessed in a BALB/c-nu mouse model bearing lung squamous carcinoma xenografts.@*RESULTS@#MTT assay showed that LCA significantly decreased the viability of H226 cells with an IC50 of 28.3 μmol/L at 48 h. Flow cytometry suggested that LCA treatment induced obvious cell cycle arrest at the G1 phase. LCA treatment also significantly decreased the expressions of cyclin D1, CDK2, and CDK4, and inhibited the phosphorylation of PI3K and Akt in H226 cells. In the tumor-bearing mice, LCA treatment for 24 days significantly reduced the tumor volume and weight.@*CONCLUSION@#LCA is capable of inhibiting the proliferation and inducing cell cycle arrest in lung squamous carcinoma cells possibility by regulating the PI3K/Akt singling pathway.