麦角甾醇类化合物G10-10A体外抗胃癌细胞MKN45生长作用的研究

Inhibitory Effect of Ergosteroids G10-10A,an Ergosteroids Compound,on Human Gastric Cancer MKN45 Cells in vitro

麦角甾醇类化合物G10-10A是从西藏高原冷杉粘褶菌(G.Abietinum)子实体中分离得到的一种麦角甾醇类化合物,本研究通过体外细胞实验观察化合物G10-10A对胃癌抗肿瘤活性及其作用机制.MTT法、生长曲线和集落形成试验显示G10-10A对人胃癌细胞MKN45有强大的抗增殖活性,流式细胞术和免疫印迹法检测G10-10A可以诱导细胞凋亡,同时增加P53及其下游P21和PUMA表达,联合小分子抑制剂Z-VAD-FMK或者Pifithrin-α能下调G10-10A诱导CL-PARP增加,减轻细胞毒活性.

Ergosteroids, a gloeophyllins A, is isolated from the fruiting bodies of Gloeophyllum abietinum collected in the Tibet plateau. In this work, the anti-tumor activity of G10-10A on gastric cancer cells is evaluated in vitro, and the underlying mechanism of action is explored. G10-10A shows robust cytotoxic activity against MKN45 cells in the MTI＂ assay, the cell growth curve assay, and the colony-formation assay. Treatment with G10-10A can in- duce the cell undergoing apoptosis in the flow cytometry assay and the western blot assay. At 24 h after treatment, G10-10A increases the protein level of P53, as well as P21 and PUMA, two downstream targets of P53. Interesting- ly, co-treatment with Small-Molecule inhibitors, Z-VAD-FMK or Pifithrin-α, attenuates the expression level of CL- PARP induced by G10-10A, and alleviates its cytotoxic activity.