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Tumor Biology

, Volume 37, Issue 8, pp 10499–10506 | Cite as

MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1

  • Di-di Wu
  • Xue-song Li
  • Xiao-Na Meng
  • Jing Yan
  • Zhi-hong Zong
Original Article

Abstract

Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P < 0.05). After predicting the miR-873 binding region in the 3′-untranslated region of ABCB1, dual-luciferase reporter assay confirmed this prediction. RT-PCR and Western blotting revealed that MDR1 expression was significantly downregulated after transfection with miR-873 and upregulated after transfection with anti-miR-873 at both mRNA and protein levels compared to negative controls (P < 0.05). Experiments in a mouse xenograft model confirmed that intratumoral administration of miR-873 could enhance the efficacy of cisplatin in inhibiting tumor growth in ovarian cancer in vivo (P < 0.05). ABCB1 overexpression reduced sensitivities of ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P < 0.05). In summary, we demonstrated that overexpression of miR-873 increased the sensitivity of ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.

Keywords

ABCB1 miR-873 Drug resistance Cisplatin Ovarian cancer 

Notes

Acknowledgements

This work was supported by Liaoning Science and Technology Grant (2013021077) and the Natural Scientific Foundation of China (No. 81472502).

Compliance with ethical standards

Conflicts of interest

None

Authors’ contributions

Z-H Z conceived the study and analyzed interpretation. D-D W, X-S L, X-N M, and JY carried out the experiments and analyzed the data. Z-H Z wrote the first and final draft of the manuscript. All authors read and approved the final manuscript.

Supplementary material

13277_2016_4944_MOESM1_ESM.doc (31 kb)
Supplementary Table 1 Primers for RT-PCR. (DOC 31 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Di-di Wu
    • 1
  • Xue-song Li
    • 1
  • Xiao-Na Meng
    • 1
  • Jing Yan
    • 1
  • Zhi-hong Zong
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, College of Basic MedicineChina Medical UniversityShenyangChina

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