氧化砷诱导胃癌细胞凋亡的信号传导途径研究

目的 检测氧化砷(As2O3)诱导胃癌细胞株(SGC-7901和MKN-45)凋亡过程中cAMP、蛋白激酶C(PKC)和酪氨酸蛋白激酶(PTK)活性变化，以探讨其诱导胃癌细胞凋亡过程中可能存在的信号传导途径。方法 应用钙离子拮抗剂、PKC和PTK抑制剂研究其对AS2O3诱导胃癌细胞凋亡过程的影响，以TUNEL法检测细胞凋亡率。以放射免疫法测定As2O3作用前后细胞内cAMP水平的变化。抽提PKC和PTK蛋白，以Lowry法测定As2O3作用前后各自蛋白表达水平的变化。结果 钙离子拮抗剂对As2O3诱导胃癌细胞凋亡过程没有影响，PKC和PTK抑制剂不仅本身能诱导胃癌细胞凋亡，且对As2O3诱导胃癌细胞凋亡具有协同作用。在As2O3诱导胃癌细胞凋亡过程中存在cAMP浓度增高和PKC、PTK活性显著降低，提示cAMP、PKC和PTK可能参与As2O3诱导胃癌细胞凋亡的作用。结论 PKC和PTK抑制剂可以通过影响信号传导系统诱导胃癌细胞凋亡，并能促进As2O3诱导胃癌细胞凋亡。

Possible signal pathway of the apoptosis in gastric cancer cell lines induced by arsenic trioxide

Objective To investigate the possible signal pathway of the apoptosis in gastric cancer cell lines(SGC 7901 and MKN 45)induced by arsenic trioxide. Methods TUNEL method was used to observe the influence of calcium antagonist, inhibitors of protein kinase C (PKC) and protein tyrosine kinase(PTK) on the apoptosis of gastric cancer cells induced by arsenic trioxide. Levels of cAMP, PKC and PTK were detected before and after the treatment with arsenic trioxide. Results Both PKC and PTK inhibitors could induce apoptosis of gastric cancer cell lines, also both of them had a cooperative action with arsenic trioxide in inducing apoptosis of gastric cancer cells, while calcium antagonist had no any effect on the apoptosis of gastric cancer cell lines. PKC and PTK levels decreased but cAMP level increased during the apoptosis of gastric cancer cells induced by arsenic trioxide ( P <0.01). PKC and PTK inhibitors can not only induce apoptosis in gastric cancer cells, but also cooperate with arsenic trioxide in inducing apoptosis of gastric cancer cells. Conclusions PKC and PTK may play an important role in the signal pathway of the apoptosis in gastric cancer cell lines induced by arsenic trioxide.