ABSTRACT
Retinoblastoma(RB)is the most common intraocular malignant tumor of children. Chemotherapy is a preferred method in RB treatment, which includes intravenous chemotherapy, intra-arterial chemotherapy and intravitreal chemotherapy. However, the occurrence of chemotherapy resistance often leads to the failure of eye-preserving treatment in RB patients. Therefore, exploring the mechanism of the occurrence of chemotherapy resistance and searching for new strategies and combined medicines for RB treatment are of great clinical significance. This article reviews that RB cells obtain chemotherapy resistance through ATP binding cassette protein(ABC transporter), non-coding RNA, epigenetics modification, autophagy, epithelial mesenchymal transformation, extracellular matrix changes and other ways, and the potential therapeutic targets for chemotherapy resistance are also summarized, in the hope of providing some references for further research on chemotherapy resistance of RB.
ABSTRACT
OBJECTIVE To study the mechanism of interfering with long non-coding RNA nicotinamide nucleotide transhydrogenase-antisense RNA1 （LncRNA NNT-AS1） expressing to reduce paclitaxel （TAX） resistance in non-small cell lung cancer （NSCLC） cells. METHODS NSCLC TAX-resistant cell line （A549/TAX） was constructed， and the expressions of LncRNA NNT-AS1 in normal， parental， and drug-resistant cells were observed. The targeting relationship of microRNA-582-5p （miR-582- 5p） with LncRNA NNT-AS1 and high mobility group box2 （HMGB2） was verified. A549/TAX cells were cultured in vitro to observe the effects of interfering with LncRNA NNT-AS1 alone or interfering with LncRNA NNT-AS1 and miR-582-5p on the expressions of LncRNA NNT-AS1 and miR-582-5p， the mRNA and protein expressions of HMGB2， cell viability， clone formation and apoptosis. The effects of interfering with LncRNA NNT-AS1 on tumor growth and the expression of miR-582-5p and the mRNA and protein expressions of HMGB2 in tumor tissue were observed in nude mice. RESULTS Compared with normal cells， LncRNA NNT-AS1 was highly expressed in parental and drug-resistant cells （P＜0.05）， showing an increasing trend. It was validated that miR-582-5p had a targeting relationship with LncRNA NNT-AS1 and HMGB2. After interfering with the expression of LncRNA NNT-AS1， the expression of LncRNA NNT-AS1 and the mRNA and protein expressions of HMGB2， cell viability and the number of cloned cells in A549/TAX cell， decreased significantly， while the expression of miR-582-5p and the apoptotic rate increased significantly （P＜0.05）； simultaneously interfering with the expression of miR-582-5p could reverse above changes （P＜ 0.05）. Interfering with the expression of LncRNA NNT-AS1 in tumor cell could significantly reduce tumor volume and tumor weight of nude mice bearing tumors； at the same time， the expression of miR-582-5p was up-regulated significantly and the mRNA and protein expressions of HMGB2 were down-regulated significantly （P＜0.05）. CONCLUSIONS Interfering with the expression of LncRNA NNT-AS1 may alleviate TAX chemotherapy resistance in NSCLC through targeted up-regulation of miR-582-5p and down-regulation of HMGB2.
ABSTRACT
Chemotherapy is currently the main clinical treatment method for malignant tumors， and chemotherapy resistance is the main factor leading to chemotherapy failure and malignant tumor recurrence and metastasis. The cha-racteristics of malignant tumors formation were regarded as similar to the “Yin Fire” theory， manifested that deficiency of original qi as the foundation of malignant tumors， imbalance of original qi and yin fire as the internal cause of malignant tumor progression， and the internal environment of phlegm-blood stasis-toxicity-deficiency caused by yin fire promoted the formation of chemoresistance. In the treatment of chemoresistance of malignant tumors， traditional Chinese medicine should focus on treating disease before its onset by tonifying the spleen and strengthening the middle， nou-rishing the original qi， and reinforcing healthy qi and anti-cancer； during the treatment， the clinicians should regulate the qi and detoxify to clear yin fire， and improve the internal environment. Summarily， the strategies were adjusting the balance of internal environment of original qi and yin fire， and conducting a comprehensive treatment during the whole process， to provide new ideas for the treatment of chemoresistance of malignant tumors with traditional Chinese medicine.
ABSTRACT
Multidrug resistance （MDR） has been a main culprit behind the failure of chemotherapy in patients with malignant tumors and a major obstacle to improving the life quality and prolonging the survival of patients. Hepatocellular carcinoma cells， the innate drug-resistant cells， are generally insensitive to radiotherapy and chemotherapy. Moreover， as the early symptoms of hepatocellular carcinoma are atypical， most patients are diagnosed at the advanced stage， with short survival period and high recurrence rate. Thus， the sensitivity to chemotherapy drugs is decreased. This explains how MDR becomes one of the important reasons for the failure of primary hepatocellular carcinoma （PHC） treatment. Therefore， it is an urgent task to search for safe and effective chemosensitizers with little adverse effect in the research on the drug resistance of hepatocellular carcinoma. As Chinese medicine has been widely applied in the treatment of tumors， the mechanisms of compound Chinese medicine prescriptions， Chinese medicine injections， and single Chinese medicinal in reversing chemotherapy resistance in liver cancer have attracted the interest of scholars. According to previous reports， the mechanisms can be summarized as increasing intracellular drug concentration， influencing changes in enzyme activity， inducing apoptosis， reversing abnormalities in cellular signaling pathways， and regulating the tumor microenvironment. Traditional Chinese medicine reduces the chemotherapy resistance of hepatocellular carcinoma cells through multiple targets and multiple pathways， thereby improving the chemotherapy sensitivity of the cancer cells and enhancing the toxicity of chemotherapeutic drugs to hepatocellular carcinoma cells. Therefore， exploring the mechanism of MDR of hepatocellular carcinoma from the perspective of traditional Chinese medicine is important for reversing the MDR and is of great reference value for clinical treatment of hepatocellular carcinoma. However， there are few experimental types and adverse effects available. Thus， the multi-mechanism and multi-target experiments and clinical research should be carried out in the future.
ABSTRACT
Because the early symptoms of ovarian cancer are not typical and there is a lack of effective screening methods， most patients are diagnosed at an advanced stage， which seriously endangers the health of modern women. Platinum-based chemotherapy after tumor reduction is the first choice for patients with advanced and recurrent ovarian cancer， but almost all patients with recurrent ovarian cancer will eventually develop platinum resistance. Therefore， the search for natural， safe， and effective chemotherapeutic sensitizers has become an urgent and important topic in the study of ovarian cancer. With the increasingly extensive application of traditional Chinese medicine （TCM） in the treatment of cancer， the research on Chinese herbal monomers is also deepening， and the mechanisms of Chinese herbal monomers in intervening in cisplatin （DDP）-induced resistance of ovarian cancer is becoming increasingly clearer. Based on the research status of Chinese herbal monomers available in many Chinese and English databases， it was found that Chinese herbal monomers were involved in the reversal of DDP-induced resistance of ovarian cancer via many routes， mainly through increasing the intracellular drug concentration， reversing the blocked apoptosis， correcting the abnormal intracellular signaling pathway， enhancing DNA damage and inhibiting DNA repair， regulating intracellular autophagy， and suppressing epithelial mesenchymal transition （EMT）. Chinese herbal monomers weaken the resistance of ovarian cancer to DDP from multiple targets and enhance the toxicity of DDP to ovarian cancer cells in vitro and transplanted tumors in vivo. Therefore， Chinese herbal monomers are expected to become natural sensitizers for ovarian cancer chemotherapy with DDP. However， the current studies on Chinese herbal monomers are still confined to the single experimental type， and their action mechanisms and toxic and side effects remain to be further clarified. The application of Chinese herbal monomers for sensitizing DDP chemotherapy still needs to be verified by multi-target， multi-level experimental studies and large-scale clinical studies in the future.
ABSTRACT
Glioma is a malignant tumor with extremely high rates of recurrence. Clinically ，with the prolongation of the use of chemotherapy drugs ，the drug resistance of glioma cells to chemotherapy drugs is also increasing ，which eventually leads to poor prognosis and shortens overall survival time of patients. It is well known that the development of drug resistance involves multiple mechanisms，including drug transport metabolism ，apoptosis，DNA damage repair ，autophagy，variation of cancer stem cells and epithelial mesenchymal transition. Abnormal expression of circular RNA （circRNA），a novel RNA molecule with unique stability and tissue specificity ，has been shown by more and more evidence to play a crucial regulatory role in the development of drug resistance in glioma. This paper systematically reviews the mechanism of multiple drug resistance in glioma ，and focuses on the role and molecular mechanism of circRNA regulating temozolomide-resistance in glioma. At the same time ，the potential function of circRNA as a new therapeutic target is prospected ，in order to provide an objective theoretical basis for the development of new therapeutic methods.
ABSTRACT
Objective To observe the expression difference of lncRNA FAL1 in ovarian cancer cells and their drug-resistant cell lines, and to explore the effect and mechanism of lncRNA FAL1 down-regulation on cell chemotherapy resistance. Methods The expression levels of fal1 gene in SKOV3 and COC1 cells and their drug-resistant cell lines were detected by qRT-PCR. fal1 siRNA was transfected to downregulate fal1 gene expression. MTT was used to detect cell proliferation. Transwell method was used to detect cell invasion ability. Plate clone formation test was used to detect cell clone ability, and Western blot was used to detect MDR-1, mpr-1, ABCG2 and phosphorylation levels of p38 MAPK, ERK1/2 and JNK. SKOV3/DDP and COC1/DDP cells transfected with FAL1-siRNA were injected subcutaneously into BALB/c nude mice. The volume and mass of subcutaneous transplanted tumors were measured. Results Compared with SKOV3 and COC1 cells, SKOV3/DDP and COC1/DDP cells were less sensitive to DDP, and the expression levels of FAL1 gene increased (P < 0.01). After transfection with FAL1-siRNA, the sensitivity of SKOV3/DDP and COC1/DDP cells to DDP increased (P < 0.01), and the invasion (P < 0.05) and cloning ability (P < 0.01) decreased. The expression levels of MDR-1, MPR-1, ABCG2 (P < 0.01) and the phosphorylation levels of p38 MAPK, ERK1/2 and JNK (P < 0.05) decreased. The volume and mass of subcutaneous transplanted tumors were significantly reduced (P < 0.01). Conclusion Down-regulation of lncRNA FAL1 could significantly reduce the chemotherapy resistance of cisplatin-resistant ovarian cancer cell lines and inhibit the proliferation of drug-resistant cells in vivo. Its mechanism is related to inhibiting the activation of MAPK signaling pathway.
ABSTRACT
Osteosarcoma (OS) is the most common primary malignant bone tumor in clinic. It has high mortality and disability rate. Effective neoadjuvant chemotherapy combined with limb salvage surgery can improve the 5-year survival rate of OS patients. Drug resistance or low sensitivity of tumor cells is the most common cause of postoperative local recurrence and metastasis. Therefore, the sensitivity of OS cells to chemotherapy drugs is of great value to the prognosis of the patients. In recent years, traditional Chinese medicine has been widely used because of high efficiency and low toxicity. A large number of studies have confirmed that part of traditional Chinese medicine can reverse the chemotherapy resistance of OS cells by regulating the ABC transmembrane transport protein system. This article gives an overview of its related mechanisms and latest developments.
ABSTRACT
Objective:To investigate the effect of long non-coding RNA (LncRNA) LINC00672 on sensitivity of breast cancer to tamoxifen and related mechanisms.Methods:Human breast cancer MCF-7 cells was treated in vitro to establish tamoxifen resistance (resistance group) and corresponding parental cell line (parent group) . The interfered LINC00672 and control cell line were constructed by Crisper-cas9 in resistant cells. (Interference 1 group, interference 2 group and control group) . The expression of LINC00672, Akt and HER2 mRNA was determined by real-time quantitative PCR. The expression levels of total Akt (Akt-pan) , phosphorylation of Akt (p-Akt) and HER2 were detected by Western blot.CCK-8 assay was used to detect cell resistance to tamoxifen.Results:The expressions of LINC00672, Akt and HER2 mRNA in the parental group were (1.000±0.086) , (1.000±0.254) and (1.000±0.208) , and the TAM IC 50 was (1.417±0.153) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the resistance group were (4.286±0.593) , (4.175±0.274) and (2.519±0.389) , and the TAM IC 50 was (12.029±1.016) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the control group were (1.000±0.093) , (1.000±0.090) and (1.000±0.097) , and the TAM IC 50 was (10.58±0.639) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the interference group 1 were (0.331±0.023) , (0.892±0.044) and (0.458±0.077) , and the TAM IC 50 was (6.250±0.836) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the interference group 2 were (0.304±0.016) , (0.919±0.050) and (0.416±0.080) , and the TAM IC 50 was (4.764±0.553) μmol/L. As compared with the parental group, the expressions of LINC00672, Akt and HER2 mRNA were significantly up-regulated ( P<0.01) in resistance group, the protein levels of Akt-pan, p-Akt and HER2 was up-regulated. The IC 50 value of tamoxifen was significantly increased in resistance group ( P<0.01) . As compared with the control group, the expression levels of LINC00672 and HER2 mRNA were significantly decreased in the interference group 1 and the interference group 2 ( P<0.01) , the levels of Akt was not significantly changed ( P>0.05) . The protein levels of p-Akt and HER2 were significantly decreased but there was no significant change in the expression of Akt-pan. The IC50 value of tamoxifen was significantly decreased ( P<0.01) . Conclusion:LINC00672 may be involved in the formation of tamoxifen resistance in breast cancer cells, and its underlying mechanism is related to the promotion of HER2/p-Akt pathway.
ABSTRACT
Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is a member of orphan nuclear receptors, which is expressed in major tissues and organs of the human body, and plays an important role in the regulation of various biological functions and gene expressions. Recent studies have shown that the expression of NR2F6 was up-regulated in a variety of malignant tumors and showed significant correlations with cancer progression. These findings triggered the widespread interest in understanding the relationship between NR2F6 and cancer development and progression. In addition, the latest studies have underscored that NR2F6 was involved in enhancing antitumor immune responses that could serve as a potential target for immune regulation. This review summarizes the biological functions of NR2F6 and its role in tumors, with the aim to provide new insights into effective cancer therapies.
Subject(s)
Humans , Gene Expression Regulation , Neoplasms/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Repressor Proteins/genetics , Transcription Factors/geneticsABSTRACT
The tumor incidence goes up with every passing year. Chemotherapy， as one of the main treatment methods， is faced with a major challenge of drug resistance in clinical practice. Tumor-associated macrophages （TAMs） are the key factors inducing chemotherapy resistance of tumors. TAMs are inflammatory cells with the largest number in the tumor microenvironment， which are widely distributed in such epithelial tissues as large intestine and stomach in the immune environment and closely associated with multiple common cancers like breast cancer and colorectal cancer. TAMs can be divided into two phenotypes， with M2-polarized TAMs into the tumor-promoting phenotype that affects the oncogenesis and progression and promotes drug resistance via immune escape， angiogenesis and other ways. At the same time， the frequently utilized chemotherapeutic agents will increase the recruitment of TAMs and trigger the secretion of cytokines， leading to the excessive polarization of macrophages to M2 type， followed by tumor drug resistance. The molecular mechanism of chemotherapy resistance is complex， which is becoming an urgent problem in the field of chemotherapy. Traditional Chinese medicine （TCM） has exhibited unique advantages in resisting tumor drug resistance. It has been proved efficient and safe in improving tumor microenvironment and regulating TAMs by acting on multiple targets via multiple ways， thus adjusting tumor progression and improving drug resistance. Based on related articles published in recent years， this paper reviewed the drug resistance-promoting effect of TAMs via regulating the immune microenvironment and interacting with tumor stem cells and the driving effect of chemotherapeutic agents on drug resistance to figure out the role of TAMs in chemotherapy resistance. Besides， it summarized the mechanisms of TCM in regulating related cytokines， proteins， activity， and the polarization direction of TAMs to expound the effective components of TCM in the intervention of drug resistance. The aim of this paper was to provide reference for further research on the biological mechanism of chemotherapy resistance and its targeted intervention with TCM.
ABSTRACT
@#[Abstract] Objective: To explore the role of miR-9-5p in the biological behaviors of breast cancer cells and its possible regulatory mechanism. Methods: online OncomiR database was used to analyze the differential expression of miR-9-5p in breast cancer tissues and normal breast tissues. qPCR was used to detect the miR-9-5p expression in breast cancer cell lines and normal breast cells. Based on target gene prediction software TargetScan, ONECUT2 (one cut homeobox 2) was predicted to be the target gene of miR-9-5p. Dual luciferase reporter system was used to validate the relationship between miR-9-5p and its promising target gene ONECUT2. MDA-231 cells were transfected with miR-9-5p mimic, ONECUT2 siRNAs as well as the corresponding control sequences. The protein and mRNA levels of stemness-associated gene NOTCH1, NANOG and SOX9 (SRY (sex-determing region of Y chromosome) -Box transcription Factor 9) were detected by WB and qPCR. The effect of transfection on proliferation, apoptosis and chemo-resistance of cells was detected by BrdU method, Annexin Ⅴ method and MTS Assay, respectively. The ALDEFLUOR experiment was used to detect the effects of miR-9-5p and its target gene ONECUT2 on tumor stemness. NSG mouse breast cancer chemotherapy model was established, and the in vivo experiments further verified the effect of ONECUT2 on tumor malignant biological behaviors, such as cell stemness and chemo-resistance. Results: miR-9-5p was highly expressed in breast cancer tissues (P=0.007) and breast cancer MDA-231 cell line (P=0.0005), and was positively correlated with the poor prognosis of breast cancer patients (P=0.0016). Compared to control group, miR-9-5p could target and negatively regulate ONECUT2 expression, further increase ALDH+ cell population (P=0.0006), as well as increase the expressions of stemness-associated genes NOTCH1, NANOG and SOX9. Besides, miR-9-5p increased the anti-apoptosis ability (P=0.0003) and chemo-resistance of MDA-231 cells; however, miR-9-5p/ONECUT2 exerted no significant effect on the proliferation ability of MDA-231 cells (P>0.05). Compared with the control group, the volume of xenografts in mice of MDA-231/ONECUT2 group after DTX chemotherapy was significantly lower than that in the control group (P<0.05), and the protein expressions of NOTCH1, SOX9 and the mRNA expression of ABC transporter in the transplanted tumor tissues were significantly reduced (P<0.05 or P<0.01). Conclusions: The highly expressed miR-9-5p in breast cancer induces tumor stemness and anti-apoptotic ability by targeting ONECUT2 and enhances its resistance to chemotherapy.
ABSTRACT
@#[Abstract] Objective: To investigate the changes in malignant biological behaviors and expression of programmed cell death-ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) YES-2 cell line after cis-dichlorodiammine platinum (CDDP) induction (YES-2/CDDP-R). Methods: YES-2 cells were treated with CDDP from low concentration to high concentration (0.25-2.0 μg/ml) with intermittent impact (15-25 days per concentration) to establish ESCC CDDP-resistant cell line YES-2/CDDP-R. The morphological change of YES-2/CDDP-R cells was observed under the inverted microscope. Methyl thiazolyl tetrazolium (MTT) was used to detect cell sensitivity to CDDP. Wound healing assay was used to detect cell migration ability. qPCR and Western blotting were used to detect mRNA and protein expressions of PD-L1. Results: After CDDP gradien ttreatment for9 months,YES-2/CDDP-R cells were successfully established. The morphology of the YES-2/CDDP-R cells showed uneven size, intracellular vacuoles and significantly increased black particles along with the appearance of huge cells. The IC50 of CDDP for YES-2/CDDP-R cells was significantly higher than that for parental cells, indicating decreased sensitivity to CDDP (P<0.05). Compared to theYES-2 cells, the proliferation and migration of YES-2/CDDP-R cells were significantly increased (P<0.05 or P<0.01), and the mRNA and protein expressions of PD-L1 were significantly up-regulated (all P<0.001). Conclusion: YES-2 cells with CDDP resistance (YES-2/CDDP-R) were successfully established. The sensitivity of YES-2/CDDP-R cells to CDDP was significantly reduced while the abilities of cell proliferation and migration were enhanced. The up-regulation of PD-L1 in YES-2/CDDP-R cells suggests that CDDP-resistance could promote immune escape by inducing PD-L1 up-regulation.
ABSTRACT
Objective@#To understand the mechanism of chemotherapy resistance in nasopharyngeal carcinoma under hypoxic conditions through the perspective of protein SUMOylation modification.@*Methods@#Cobalt chloride (CoCl2) was used to establish the hypoxic model of human nasopharyngeal carcinoma CNE1 cells. Then, the cell cycle was detected by flow cytometry, and the expression level of small ubiquitin-related modifier(SUMO) and cyclin-dependent kinase 6 (CDK6) proteins were detected by western blotting. MTT assay was used to determine the median lethal dose (IC50) of cancer cells against cisplatin, and enzyme-linked immunosorbent assay (ELISA) was used to determine lactate dehydrogenase (LDH) level.@*Results@#The cell cycle of CNE1 induced by hypoxia was arrested in G0/G1 phase.The results of Western blot showed that the protein expression level of CDK6 in CNE1 cells was lower than that in the control group (0.83±0.25 vs. 0.43±0.21, t=14.67, P=0.003). The protein level of conjugated SUMO1 was significantly lower than that in the control group (2.69±0.48 vs. 1.38±0.31, t=17.22, P=0.001), while the level of free SUMO1 protein was significantly higher than that in the control group (2.01±0.43 vs. 2.60±0.59, t=15.45, P=0.002).The LC50 of CNE1 cells in the control group was significantly lower than that in the hypoxic group (29.44 μg/ml vs. 97.72 μg/ml, t=12.79, P=0.001). After CNE1 cells received 50 μg/ml cisplatin for 48 h, the LDH content in the supernatant of the control group was significantly higher than that in the hypoxic group ((541.49±64.59) ng/ml vs. (234.67±41.03) ng/ml, t=11.94, P=0.007)). The apoptosis rate of CNE1 cells in the control group was significantly higher than that in the hypoxic group ((76.64±5.37)% vs. (32.84±4.77) ng/ml, t=8.49, P=0.003)).@*Conclusion@#Hypoxia can dissociate the covalent modification of CDK6 and SUMO1, inhibit cell cycle and increase the chemotherapy resistance of nasopharyngeal carcinoma.
ABSTRACT
@# Objective: To investigate the role and molecular mechanism of miR-520d in reversing the chemoresistance of triple negative breast cancer (TNBC) by regulating autophagy. Methods: Docetaxel (Doc) resistant cell lines MDA-MB-231/Doc and MDA-MB468/Doc were constructed by using human TNBC cell lines MDA-MB-231 and MDA-MB-468 as parental cells, and the cells were divided into blank group (parental cells), control group (drug-resistant group), and miR-520d over-expression group. The expression levels of miR-520d in cells of the blank and drug-resistant groups were detected by qPCR. The Doc-sensitivity of resistant cells over-expressing miR-520d was detected by MTT assay.After MDC staining, the generation of autophagosome in cells was observed under fluorescence microscopy; the number of miR-520d over-expressed resistant cells with positive LC3 expression was observed under confocal microscopy. The luciferase reporter gene assay was used to verify the targeting relationship between miR-520d and Beclin1. The effect of miR-520d mimics on the expression of autophagy-associated protein Beclin1, and LC3Ⅰ, LC3Ⅱ in cells was detected by WB assay. Results: The results of qPCR showed that the expression of miR-520d in the drug-resistant TNBC cells was significantly lower than that of normal cells (P<0.01). In drug-resistant cells over-expressing miR-520d, the Doc-sensitivity was significantly improved, while the autophagy activity was significantly reduced (all P<0.01).At the same time, luciferase experiments demonstrated that Beclin1 was a possible target molecule of miR-520d (P<0.05). WB results showed that the combination of docetaxel and miR-520d mimics reduced the LC3-II/I ratio and the expression of autophagy protein Beclin1 in drug-resistant TNBC cells (all P<0.05). Conclusion: The regulation of miR-520d levels may alter the expression of autophagy protein Beclin1, thereby reversing Doc chemotherapy resistance in TNBC cells.
ABSTRACT
Objective@#Our study aimed to investigate the effect of histone deacetylase inhibitor trichostatin A（TSA）on the cisplatin（CDDP） resistance of ovarian cancer cell lines and its molecular mechanism.@*Methods@#Cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008 were incubated with TSA（200 nmol/L） or/and CDDP（20 μmol/L），the inhibitory rate of tumor cells was determined by MTT assay. Flow cytometry and Western blotting were used to detect apoptosis of tumor cells. Western blotting was also used to detect STAT3 expression in C13* and OV2008 cells. After down-regulation of STAT3 by transfection of STAT3 siRNA in C13* cells，cisplatin-induced apoptosis was evaluated by flow cytometry.@*Results@#MTT assay showed that the proliferation inhibitory rates of the combination group after 48 or 72 h treatment were significantly higher than those of TSA and CDDP groups. The level of STAT3 protein was much higher in C13* cells than in OV2008 cells. Flow cytometry and Western blotting showed that TSA combined with CDDP significantly enhanced the apoptotic rate of C13* cells. STAT3 expression level was significantly higher in C13* cells than in OV2008. Downregulation of STAT3 can significantly improve CDDP-induced apoptosis of C13* cells. @*Conclusion@#Down-regulation of STAT3 by TSA endows cisplatin-resistant cells C13* with increased sensitivity to cisplatin.
ABSTRACT
Gastric cancer is a serious malignancy that endangers human health. Increased rates of chemotherapy-resistant cancer have led to a decrease in the efficacy of treatment. Recent studies found that the presence of hypoxia in the tumor microenvironment was a notable cause of gastric cancer resistance to chemotherapy drugs. The abnormal structure and function of blood vessels in the tumor and the rapid proliferation of tumor cells increase the oxygen consumption of tumor cells, which results in tumor tissue hypox-ia. Hypoxic conditions make tumor cells more aggressive, more likely to metastasize and develop resistance to chemotherapy. In this paper, we have reviewed the progress of research into hypoxia-induced chemotherapeutic drug resistance in gastric cancer. The review has covered the causes of hypoxia and the characteristics of the hypoxic microenvironment in gastric cancer, the current situation and causes of hypoxia-induced chemotherapeutic drug resistance in gastric cancer, and the measures to overcome the hypoxia-induced re-sistance to chemotherapy drugs.
ABSTRACT
Objective The objective of this study was to investigate the clinical value of serum microRNA in predicting chemotherapy efficacy in patients with nasopharyngeal carcinoma. Methods A total of 187 patients with nasopharyngeal carcinoma who received cisplatin combined chemotherapy were enrolled in our hospital from January 2010 to December 2016,including 123 pa-tients with chemotherapy sensitivity and 64 patients with chemotherapy resistance. The serum levels of miRNA before the initial chem-otherapy were measured,the efficacy and predictive value of serum miRNA in nasopharyngeal carcinoma patients were evaluated using healthy subjects as controls. Results Serum level of miR-127 in nasopharyngeal carcinoma patients was significantly higher than that in healthy controls(4. 3 ± 1. 6 vs. 1. 4 ± 0. 5,P<0. 001). Serum level of miR-127 was significantly higher in chemotherapy-resistant patients than that in chemotherapy-sensitive patients(4. 5 ± 1. 3 vs. 3. 8 ± 1. 7,P<0. 001). The ROC curve showed that the predictive value of serum miR-127 for chemotherapy resistance in nasopharyngeal carcinoma patients was 0. 702(P<0. 001), with the optimal cut-off value of 4. 2,sensitivity of 82. 3% and specificity of 76. 3% . Compared with the chemotherapy-sensitive group,the proportion of patients with T3-4 ,N3 and TNM Ⅲ~Ⅳ in the chemotherapy-resistant group was significantly increased(P<0. 01),and the proportion of miR-127≥4. 2 was also increased(P<0. 001). Multivariate logistic regression analysis showed that TNM staging(OR=1. 655,95% CI:1. 142~2. 584,P=0. 016)and serum miR-127≥4. 2(OR=2. 231,95% CI:1. 762~4. 503,P=0. 001)were independent risk factors affecting chemotherapy resistance in nasopharyngeal carcinoma patients. Conclusion The el-evated serum level of miR-127 is an important risk factor for predicting chemotherapy resistance in patients with nasopharyngeal car-cinoma.
ABSTRACT
Single cell sequencing developed in recent years,which studies genome and transcriptome at single cell level,is more suitable for solving problems on minor special sample studies,heterogenous population analysis and finding concurrent or mutually exclusive genomic events,compared to bulk sequencing.For breast cancer,which is highly heterogeneous,bulk sequencing data is not enough for solving many clinical problems,and single cell sequencing precisely plays an important role in it.This review,focusing on a minor special cell population in breast cancer (such as cancer stem cells,circulating tumor cells,et al),tumor heterogeneity and clonal evolution,and chemotherapy resistance,summarized application of single cell sequencing in breast cancer research in recent years,and discussed the future research directions.
ABSTRACT
OBJECTIVE To explore the mechanism of Aurora kinase A (Aurora-A) promoting cancer cell chemotherapy resistance in nasopharyngeal carcinoma. METHODS The expression of Aurora-A in nasopharyngeal carcinoma tissues and adjacent tissues were detected by Western bolt and Q-PCR. The highexpressing Aurora A cell line CNE2 was used to detected the cell apoptosis and the expression of key pathway marker protein after Aurora-A inhibitor VX680 and cisplatin treatment by using Flow cytometry and WB. RESULTS The expression of Aurora-A in nasopharyngeal carcinoma tissues was significantly higher than that in adjacent tissues. Comparing to normal nasopharyngeal cells NP69, Aurora-A was significantly highly expressed in all of nasopharyngeal carcinoma cells and was highest in CNE2. Inhibiton of Aurora-A increased the cell apoptosis and the expression of p-AKT, p21 and Cleaved-Caspase-3 after using cisplatin or the Aurora-A inhibitor VX680 treatment. CONCLUSION The results shown that Aurora-A confer chemoresistance to cisplatin treatment through p-AKT/p21/Cleaved-Caspase-3 pathway.