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目的:观察P38磷酸化水平对胃癌细胞微管聚合的影响,探讨三氧化二砷(As2O3)通过P38磷酸化调节胃癌顺铂耐药细胞凋亡的机制。方法:通过对亲本敏感胃癌细胞株SGC7901细胞长期低剂量诱导建立胃癌顺铂耐药细胞株SGC7901/DDP,CCK-8和流式细胞术检测其对As2O3的耐受程度。通过抑制SGC7901细胞内P38的磷酸化水平,观察在As2O3处理下细胞微管蛋白的聚合程度和耐药性的改变。结果:CCK-8和AV-PI结果表明,SGC7901/DDP相对于SGC7901对As2O3具有显著的耐受性。磷酸化P38的表达在SGC7901/DDP细胞经As2O3处理时被显著抑制,这与SGC7901/DDP细胞中微管的稳定性密切相关。As2O3处理细胞时,抑制SGC7901细胞中P38的磷酸化能显著减少细胞中微管的聚合和凋亡。结论:SGC7901/DDP细胞对As2O3的耐受性与细胞内P38磷酸化水平有关,微管聚合是胃癌细胞耐受As2O3的重要机制。
AIM: To investigate the effect of P38 phosphorylation on microtubule polymerization in gastric cancer cells and to explore the mechanism of arsenic trioxide (As2O3) regulating the apoptosis of cisplatin-resistant cells by P38 phosphorylation. Methods: The gastric cancer cisplatin-resistant cell lines SGC7901 / DDP, CCK-8 and flow cytometry were used to detect the tolerance of As2O3 to long-term low-dose induction of SGC7901 cells. By inhibiting the phosphorylation level of P38 in SGC7901 cells, we observed the changes of the degree of polymerization and drug resistance of tubulin in As2O3-treated cells. Results: The results of CCK-8 and AV-PI showed that SGC7901 / DDP was significantly tolerant to As2O3 as compared to SGC7901. The phosphorylation of P38 was significantly inhibited in SGC7901 / DDP cells treated with As2O3, which is closely related to the stability of microtubules in SGC7901 / DDP cells. Inhibition of P38 phosphorylation in SGC7901 cells significantly reduced microtubule aggregation and apoptosis in cells treated with As2O3. Conclusion: The tolerance of As2O3 to SGC7901 / DDP cells is related to the level of intracellular P38 phosphorylation. Microtubule polymerization is an important mechanism of gastric cancer cells to tolerate As2O3.