Tags

Type your tag names separated by a space and hit enter

MicroRNA-133b targets glutathione S-transferase π expression to increase ovarian cancer cell sensitivity to chemotherapy drugs.
Drug Des Devel Ther. 2015; 9:5225-35.DD

Abstract

BACKGROUND

Accumulating studies reveal that aberrant microRNA (miRNA) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. The aim of this study was to investigate the role of miR-133b in the development of drug resistance in ovarian cancer cells.

METHODS

We examined the levels of miR-133b expression in ovarian carcinoma tissues and the human ovarian carcinoma cell lines (A2780, A2780/DDP and A2780/Taxol, respectively). We determined the cell viability of these cell lines treated with cisplatin or paclitaxel in the presence or absence of miR-133b or anti-miR-133b transfection using the MTT assay. Reverse transcription polymerase chain reaction and Western blotting were used to assess the mRNA and protein expression levels of two drug-resistance-related genes: glutathione S-transferase (GST)-π and multidrug resistance protein 1 (MDR1). The dual-luciferase reporter assay was used to detect the promoter activity of GST-π in the presence and absence of miR-133b.

RESULTS

The expression of miR-133b was significantly lower in primary resistant ovarian carcinomas than in the chemotherapy-sensitive carcinomas (P<0.05), and the same results were found in primary resistant ovarian cell lines (A2780/Taxol and A2780/DDP) compared to the chemotherapy-sensitive cell line (A2780; P<0.05). Following miR-133b transfection, four cell lines showed increased sensitivity to paclitaxel and cisplatin, while anti-miR-133b transfection reduced cell sensitivity to paclitaxel and cisplatin. Dual-luciferase reporter assay showed that miR-133b interacted with the 3'-untranslated region of GST-π. Compared to controls, the mRNA and protein levels of MDR1 and GST-π were downregulated after miR-133b transfection and upregulated after anti-miR-133b transfection.

CONCLUSION

MicroRNA-133b may reduce ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GST-π and MDR1. In future, the combination of miR-133b with chemotherapy agents may prevent the development of drug resistance in ovarian cancers.

Authors+Show Affiliations

Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.Department of Gynecology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, People's Republic of China.Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26396496

Citation

Chen, Shuo, et al. "MicroRNA-133b Targets Glutathione S-transferase Π Expression to Increase Ovarian Cancer Cell Sensitivity to Chemotherapy Drugs." Drug Design, Development and Therapy, vol. 9, 2015, pp. 5225-35.
Chen S, Jiao JW, Sun KX, et al. MicroRNA-133b targets glutathione S-transferase π expression to increase ovarian cancer cell sensitivity to chemotherapy drugs. Drug Des Devel Ther. 2015;9:5225-35.
Chen, S., Jiao, J. W., Sun, K. X., Zong, Z. H., & Zhao, Y. (2015). MicroRNA-133b targets glutathione S-transferase π expression to increase ovarian cancer cell sensitivity to chemotherapy drugs. Drug Design, Development and Therapy, 9, 5225-35. https://doi.org/10.2147/DDDT.S87526
Chen S, et al. MicroRNA-133b Targets Glutathione S-transferase Π Expression to Increase Ovarian Cancer Cell Sensitivity to Chemotherapy Drugs. Drug Des Devel Ther. 2015;9:5225-35. PubMed PMID: 26396496.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-133b targets glutathione S-transferase π expression to increase ovarian cancer cell sensitivity to chemotherapy drugs. AU - Chen,Shuo, AU - Jiao,Jin-Wen, AU - Sun,Kai-Xuan, AU - Zong,Zhi-Hong, AU - Zhao,Yang, Y1 - 2015/09/16/ PY - 2015/9/24/entrez PY - 2015/9/24/pubmed PY - 2016/7/7/medline KW - cisplatin KW - drug resistance KW - ovarian cancer cells KW - paclitaxel SP - 5225 EP - 35 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 9 N2 - BACKGROUND: Accumulating studies reveal that aberrant microRNA (miRNA) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. The aim of this study was to investigate the role of miR-133b in the development of drug resistance in ovarian cancer cells. METHODS: We examined the levels of miR-133b expression in ovarian carcinoma tissues and the human ovarian carcinoma cell lines (A2780, A2780/DDP and A2780/Taxol, respectively). We determined the cell viability of these cell lines treated with cisplatin or paclitaxel in the presence or absence of miR-133b or anti-miR-133b transfection using the MTT assay. Reverse transcription polymerase chain reaction and Western blotting were used to assess the mRNA and protein expression levels of two drug-resistance-related genes: glutathione S-transferase (GST)-π and multidrug resistance protein 1 (MDR1). The dual-luciferase reporter assay was used to detect the promoter activity of GST-π in the presence and absence of miR-133b. RESULTS: The expression of miR-133b was significantly lower in primary resistant ovarian carcinomas than in the chemotherapy-sensitive carcinomas (P<0.05), and the same results were found in primary resistant ovarian cell lines (A2780/Taxol and A2780/DDP) compared to the chemotherapy-sensitive cell line (A2780; P<0.05). Following miR-133b transfection, four cell lines showed increased sensitivity to paclitaxel and cisplatin, while anti-miR-133b transfection reduced cell sensitivity to paclitaxel and cisplatin. Dual-luciferase reporter assay showed that miR-133b interacted with the 3'-untranslated region of GST-π. Compared to controls, the mRNA and protein levels of MDR1 and GST-π were downregulated after miR-133b transfection and upregulated after anti-miR-133b transfection. CONCLUSION: MicroRNA-133b may reduce ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GST-π and MDR1. In future, the combination of miR-133b with chemotherapy agents may prevent the development of drug resistance in ovarian cancers. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/26396496/MicroRNA_133b_targets_glutathione_S_transferase_π_expression_to_increase_ovarian_cancer_cell_sensitivity_to_chemotherapy_drugs_ L2 - https://dx.doi.org/10.2147/DDDT.S87526 DB - PRIME DP - Unbound Medicine ER -