胶霉毒素通过PI3K/AKT/mTOR抑制食管癌细胞增殖

Gliotoxin Inhibits the Growth of Esophageal Cancer Cells through PI3K/AKT/mTOR Axis

摘要: 目的：胶霉毒素抑制食管癌细胞增殖及其作用机制研究。方法：分别购买3种食管癌细胞系EC9706、EC109及KYSE-150，随后通过不同浓度胶霉毒素(0, 1, 5, 10, 20, 40 μM)处理三种细胞系。克隆形成检测三种食管癌细胞在胶霉毒素处理后其细胞克隆形成能力变化。流式细胞术检测胶霉毒素处理后食管癌细胞的凋亡情况。Western Blot检测食管癌细胞中PI3K/AKT/mTOR通路信号相关蛋白及凋亡相关蛋白表达水平。结果：EC9706、EC109及KYSE-150细胞通过不同浓度胶霉毒素10 μM、20 μM处理后发现胶霉毒素浓度的升高能显著提升抑制食管癌细胞的克隆形成能力。不同时间段检测细胞凋亡结果表明在相同浓度胶霉毒素处理的条件下，处理48小时后的细胞凋亡率比处理24小时的更高，而随着胶霉毒素浓度增加，细胞凋亡率也明显增加。另一方面，10 μM与20 μM胶霉毒素处理后的食管癌细胞中PI3K/AKT/mTOR信号通路中相关蛋白的表达水平都被显著抑制，而20 μM处理得更为明显。结论：胶霉毒素能够通过PI3K/AKT/mTOR通路抑制食管癌细胞增殖，并促进食管癌细胞中凋亡蛋白表达，有效阻止食管癌的恶化。

Abstract: Objective: To study the effect of gliotoxin on the growth of esophageal cancer (EC) cells and its mechanism. Methods: Three EC cell lines (EC9706, EC109 and KYSE-150) were purchased and treated with different concentrations of gliotoxin (0, 1, 5, 10, 20, and 40 μM). Colony formation assay to detect the clone formation ability, flow cytometry to detect apoptosis, and Western Blot to detect the levels of PI3K/AKT/mTOR pathway signaling-related proteins and apoptosis-related proteins in EC cells. Results: The increase in gliotoxin concentration significantly inhibited colony formation of EC9706, EC109, and KYSE-150 cells, which was most obvious at 10 μM and 20 μM. The apoptosis rate of cells treated for 48 hours was higher than that of cells treated for 24 hours under the same concentration of gliotoxin, and the apoptosis rate increased significantly with gliotoxin concentration. The PI3K/AKT/mTOR pathway was inhibited by 10 μM and 20 μM gliotoxin, with 20 μM treatment being more pronounced. Conclusion: Gliotoxin can inhibit EC cell proliferation through the PI3K/AKT/mTOR pathway, thereby promoting the expression of apoptosis protein in esophageal cancer cells and effectively preventing EC progression.