[Regulatory effects and associated mechanisms of miR-130a molecules on cisplatin resistance in ovarian cancer A2780 cell lines].
OBJECTIVE
To determine the regulatory effects and associated mechanisms of miR-130a on cisplatin resistance in ovarian cancer A2780 cell lines (including cisplatin sensitive A2780s and its resistant A2780/DDP cells).


METHODS
A2780s and A2780/DDP cells were divided into four groups, and treated with lipo2000 (Lip), miR-negative (miR-NC) control, miR-130a-mimics (miR-130a-M increasing the expression of miR-130a and the agent), and miR-130a-inhibitor (miR-130a-I downregulating miR-130a expression), respectively. The proliferation of cells and their sensitivity to cisplatin were detected by MTT assay. RT-PCR and western blot were performed to examine the levels of MDR1, PTEN mRNA and proteins.


RESULTS
The expressions of MDR1 mRNA and P-gp in the A2780/DDP cells were significantly higher than those in the A2780s cells. However, no differences in the expressions of PTEN mRNA and proteins were detected between the two cell lines. Over-expressions of miR-130a had no effect on cell proliferation, but increased the resistance of the cells to cisplatin and up-regulated the expressions of MDR1 mRNA and P-gp in both cell lines. Down-regulated miR-130a did not affect cell proliferations, but enhanced the sensitivity of the cells to cisplatin, inhibited the expressions of MDR1 mRNA and P-gp and increased the expression of PTEN proteins.


CONCLUSIONS
MiR-130a expression may be associated with cisplatin resistance of ovarian cancer cells. MiR-130a inhibitor can reverse the cisplatin resistance by upregulating the expression of PTEN proteins and down-regulating P-gp in A2780 cell lines. MiR-130 may become a new potential target of genetic therapy for cisplatin-resistant ovarian cancers.
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Ning-wei
NW
Li
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Hong-Jing
HJ
Wang
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Ling-Yun
LY
Yang
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Xi-Biao
XB
Jia
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Cen
C
Chen
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Xue
X
Wang
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D002945:Cisplatin