Modulation of Drug Resistance in Ovarian Cancer Cells by Inhibition of Protein Kinase C-alpha (PKC-alpha) with Small Interference RNA (siRNA) Agents

Objective: To determine whether silence of PKC-alpha expression by small interference RNA (siRNA) might regulate MDR1 expression and reverse chemoresistance of ovarian cancer. Methods: We measured gene and protein expression of MDR1 and PKC-alpha in ovarian cancer cells and assessed their correlation with cell drug resistance. We also examined whether blocking PKC-alpha by RNA interference (RNAi) affected MDR1 expression and reversed drug resistance in drug sensitivity tests. Results: The drug resistance cell lines, OV1228/DDP and OV1228/Taxol, had higher gene and protein expression of MDR1 and PKC-alpha than their counterpart sensitive cell line, OV1228. SiRNA depressed PKC-alpha gene protein expression, as well as MDR1 and protein expression and improved the drug sensitivity in OV1228/DDP and OV1228/Taxol cells. Conclusion: These results indicated that decreasing PKC-alpha expression with siRNA might be an effective method to improve drug sensitivity in drug resistant cells with elevated levels of PKC-alpha and MDR1. A new siRNA-based therapeutic strategy targeting PKC-alpha gene could be designed to overcome the chemoresistance of ovarian cancer.