Pharmacological Inhibition of Protein Kinase C Activity Could Induce Apoptosis in Gastric Cancer Cells by Differential Regulation of Apoptosis-Related Genes
Pharmacological Inhibition of Protein Kinase C Activity Could Induce Apoptosis in Gastric Cancer Cells by Differential Regulation of Apoptosis-Related Genes
复制标题
DOI：
10.1023/a:1026670301787
复制
发表时间：
1999-10
影响因子：
3.1
通讯作者：
G. Zhu;B. Wong;M. Eggo;S. Yuen;K. Lai;S. Lam
中科院分区：
文献类型：
--
作者：
G. Zhu;B. Wong;M. Eggo;S. Yuen;K. Lai;S. Lam
蛋白激酶C （PKC）信号通路在肿瘤细胞增殖、分化和凋亡中起关键作用。胃癌通常比正常组织具有更高水平的PKC活性。我们评估了PKC活性在诱导胃癌细胞凋亡中的抑制作用以及凋亡相关基因的表达谱。用两种高度特异性的PKC抑制剂（RO-31-8220和chelerythrine）培养胃癌细胞（AGS）。分别用甲基四氮唑（MTT）法和流式细胞术测定细胞活力和细胞周期。用吖啶橙染色、DNA凝胶电泳和流式细胞术检测细胞凋亡。western blot检测p53、p21waf/cip1、c-myc、bcl-2、bax的表达。结果表明，两种pkc抑制剂均能抑制细胞生长，阻滞g0 / g1期细胞，诱导细胞凋亡。药物暴露后p53、p21waf/cip1、c-myc、bax蛋白水平升高，而bcl-2保持不变。综上所述，PKC抑制剂通过诱导胃癌细胞凋亡和细胞周期静止来抑制胃癌细胞的生长，这可能与凋亡相关基因的差异表达有关。
The protein kinase C (PKC) signaling pathwayplays a key role in tumor cell proliferation,differentiation, and apoptosis. Gastric cancer usuallypossesses a higher level of PKC activity than normaltissue. We evaluated inhibition of PKC activity inapoptosis induction of gastric cancer cells and theexpression profile of apoptosis-related genes. Gastriccancer cells (AGS) were incubated with two highlyspecific PKC inhibitors (RO-31-8220 and chelerythrine).Cell viability and cell cycle were determined bymethyl-tetrazolium (MTT) assay and flow cytometry,respectively. Apoptosis was characterized by acridineorange staining, DNA gel electrophoresis, and flowcytometry. The expression of p53,p21waf/cip1, c-myc, bcl-2, and bax wasdetermined by western blot. The results showed that bothPKC inhibitors hindered cell growth, arrested cells atG0/G1phase and induced apoptosis.The protein level of p53, p21waf/cip1, c-myc,and bax was elevated while bcl-2 kept unchangedfollowing drug exposure. In conclusion, PKC inhibitorssuppress growth of gastric cancer cells throughapoptosis induction and cell cycle quiescence, which maybe regulated by differential expression ofapoptosis-related genes.