Modulation of drug resistance in ovarian cancer cells by inhibition of protein kinase C-alpha (PKC-α) with small interference RNA (siRNA) agents.

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