首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Overexpression of protein kinase Cdelta enhances cisplatin-induced cytotoxicity correlated with p53 in gastric cancer cell line.
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Overexpression of protein kinase Cdelta enhances cisplatin-induced cytotoxicity correlated with p53 in gastric cancer cell line.

机译:蛋白激酶Cdelta的过表达增强了顺铂诱导的与胃癌细胞株中p53相关的细胞毒性。

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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) delta is known as a positive regulator for cisplatin-induced cell death. In our present study, we examined whether overexpression of PKCdelta 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 PKCdelta and p53 after exposure to cisplatin. In addition, the active form of caspase-3 was detected by Western blotting. RESULTS: Overexpression of exogenous PKCdelta did not induce cell death in MKN28 but inhibited cell growth at 1 microg/ml cisplatin as compared to that by cisplatin alone. Moreover, overexpression of both wild-type p53 andexogenous PKCdelta in MKN28 increased cisplatin-induced cell death in MKN28. CONCLUSION: These results suggest that PKCdelta, in cooperation with p53, possibly regulates cisplatin-induced caspase-3-mediated cell death in gastric cancer.
机译:目的:研究癌症对顺铂等抗癌药物的细胞敏感性机制是癌症治疗中的一个重要问题。顺铂是一种破坏DNA的药物,包括p53在内的多种因素与癌症中对顺铂的敏感性有关。蛋白激酶C(PKC)δ被称为顺铂诱导的细胞死亡的正调节剂。在我们目前的研究中,我们检查了PKCdelta和p53的过表达是否增加了人胃癌细胞系MKN28对顺铂的敏感性,MKN28具有p53基因的突变。方法:检测MKN28在腺病毒介导的顺铂作用下PKCdelta和p53表达的细胞活力和DNA含量。另外,通过Western印迹检测了caspase-3的活性形式。结果:与单独使用顺铂相比,过表达外源性PKCdelta不会在MKN28中诱导细胞死亡,但是可以抑制细胞生长(1微克/毫升顺铂)。此外,MKN28中野生型p53和外源性PKCdelta的过度表达增加了顺铂诱导的MKN28细胞死亡。结论:这些结果表明,PKCdelta与p53协同调节胃癌中顺铂诱导的caspase-3介导的细胞死亡。

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