Overexpression of Protein Kinase Cδ Enhances Cisplatin-Induced Cytotoxicity Correlated with p53 in Gastric Cancer Cell Line

Abstract

Objective: An important issue in cancer therapy is to investigate the mechanism for cellular sensitivity to anticancer agents such as cisplatin. Cisplatin is one of the DNA-damaging agents and several factors including p53 are related to the sensitivity to cisplatin in cancer. Protein kinase C (PKC) δ is known as a positive regulator for cisplatin-induced cell death. In our present study, we examined whether overexpression of PKCδ and p53 increases the sensitivity of the human gastric cancer cell line, MKN28, which has a mutation of p53 gene, to cisplatin. Methods: Cell viability and DNA content were measured in MKN28 with adenovirus-mediated expression of PKCδ and p53 after exposure to cisplatin. In addition, the active form of caspase-3 was detected by Western blotting. Results: Overexpression of exogenous PKCδ did not induce cell death in MKN28 but inhibited cell growth at 1 µg/ml cisplatin as compared to that by cisplatin alone. Moreover, overexpression of both wild-type p53 and exogenous PKCδ in MKN28 increased cisplatin-induced cell death in MKN28. Conclusion: These results suggest that PKCδ, in cooperation with p53, possibly regulates cisplatin-induced caspase-3-mediated cell death in gastric cancer.