The Role Of Mitochondrial Dynamics Related Proteins In The Resistance Of Ovarian Cancer Cell SKOV3 To Cisplatin And Its Underlying Mechanism

Objective:In the present study,we investigated the role of mitochondrial dynamics in cisplatin resistance in ovarian cancer to lay a new theoretical foundation for the chemotherapy effect and cute rate of ovarian cancer,which may provide possible new therapeutic target to prevent cisplatin resistance in ovarian cancer.Method:In our study,we choosed the human ovarian epithelial carcinoma cell line(SKOV3)and cisplatin resistant human ovarian cancer cell line(SKOV3/DDP).To simulate ciaplatin resistance in ovarian cancer,we carried out the experiment of cisplatin stress in SKOV3 and observed mitochondrial dynamic related proteins expression.To further investigate the role of mitochondrial fusion in the resistance of ovarian cancer to cisplatin and its underlying mechanism,we knocked down Mfn 2 in SKOV3/DDP by siRNA interference.Cells in experimental group were given the cisplatin treatment to be detected after 24 hours.Firstly,we measured the changes in mitochondrial membrane potential by staining the cells with TMRE and made quantitative analysis by flow cytometer.Next,we detected the intracellular ROS by DCFH-DA fluorescent probe and made quantitative analysis by flow cytometer.Besises,we investigated the expression of Bcl-2 family member Bax and the activation of Caspase-9 and Caspase-3.Finally,we isolated mitochondria and detected the Cytochro-me C release.Results:Compared with the human ovarian epithelial carcinoma cell line(SKOV3),the mitochondrial fusion proteins were markedly up-regulated in SKOV3/DDP cells,and mitochondrial fission proteins were markedly down-regulated.This result was consistent with the effect of cisplatin stress on mitochondrial dynamic related proteins expression.We found knockdown Mfn 2 in SKOV3/DDP by siRNA interference increased the sensitivity of SKOV3/DDP cells to cisplatin,which was shown via decreased mitochondrial membrane potential and increased the release of ROS,increased the expression of Bax,increased release of Cytochrome C and activation of Caspase-dependent apoptotic pathway.Conclusion:Mitochondrial dynamics might be involved in cisplatin resistance in ovarian cancer,which will help to find a new therapeutic target for cisplatin resistance in ovarian cancer and provide a reference for the treatment of ovarian cancer.