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


Objective: To determine whether silence of PKC-α expression by small interference RNA (siRNA) mightregulate MDR1 expression and reverse chemoresistance of ovarian cancer.
Methods: We measured gene andprotein expression of MDR1 and PKC-α in ovarian cancer cells and assessed their correlation with cell drugresistance. We also examined whether blocking PKC-α by RNA interference (RNAi) affected MDR1 expressionand reversed drug resistance in drug sensitivity tests.
Results: The drug resistance cell lines, OV1228/DDP andOV1228/Taxol, had higher gene and protein expression of MDR1 and PKC-α than their counterpart sensitivecell line, OV1228. SiRNA depressed PKC-α gene protein expression, as well as MDR1 and protein expressionand improved the drug sensitivity in OV1228/DDP and OV1228/Taxol cells.
Conclusion: These results indicatedthat decreasing PKC-α expression with siRNA might be an effective method to improve drug sensitivity in drugresistant cells with elevated levels of PKC-α and MDR1. A new siRNA-based therapeutic strategy targetingPKC-α gene could be designed to overcome the chemoresistance of ovarian cancer.