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

  • Zhao, Li-Jun (Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital & Institute, Nanjing Medical University) ;
  • Xu, Heng (Center for Biotechnology and Genomic Medicine (CBGM), Georgia Health Sciences University) ;
  • Qu, Jun-Wei (Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital & Institute, Nanjing Medical University) ;
  • Zhao, Wan-Zhou (Sino-EU Biomedical Innovation Center (SEBIC), OG Pharma Corporation) ;
  • Zhao, Yi-Bing (Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital & Institute, Nanjing Medical University) ;
  • Wang, Jin-Hua (Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital & Institute, Nanjing Medical University)
  • Published : 2012.08.31


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.


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