摘要
目的探讨藤黄酸(GA)对细胞表面转铁蛋白受体(TFR)表达差异的SPC-A-1肺腺癌、SK-MES-1肺鳞癌细胞的促凋亡作用及其诱导其凋亡的分子机制。方法采用免疫组化法检测SPC-A-1及SK-MES-1 2组肺癌细胞表面TFR的表达,采用流式细胞术检测不同浓度的GA作用于两组肺癌细胞24 h后细胞的凋亡率;并通过Western-blotting检测不同浓度的GA作用于2组细胞后Caspase2、Caspase9、Caspase10及促凋亡蛋白Bax、p53的表达。结果 GA对2组肺癌细胞有明显的促凋亡作用。相同浓度下细胞表面TFR表达强的SPC-A-1细胞对GA诱导其凋亡的敏感性高。凋亡起始酶Caspase2、Caspase9、Caspase10及促凋亡蛋白Bax、p53的表达都参与了GA诱导的肺癌细胞凋亡,且随着GA浓度增大表达均上调。结论 GA通过与TFR组成配体,诱导SPC-A-1及SK-M ES-1细胞凋亡,内外源性凋亡通路都参与了GA诱导的SPC-A-1及SK-MES-1细胞凋亡;GA是一种高效的、有着广泛前景的抗肿瘤药物。
Objective To investigate the apoptosis along with its molecular mechanism caused by Gambogic acid （GA） in SPC-A-1 lung adencarcinoma cells and SK-MES-1 lung squamous cancer cells which are on their surface with different TFR expressions. Methods Immunohistochemi- cal method was used to measure the expression levels of TFR on the surface of two types of lung cancer cells. Flow cytometry were used to detect the apoptosis of SPC-A-1 and SK-MES-1 ceils induced for 24 hours by GA respectively. Western blotting was used to detect the changes of Caspase2, Caspase9, Caspasel0 and Bax, p53 in protein expressive levels affected by GA. Results The lung cells were promoted in apoptosis by the effect of GA. The sensitivity of the SPC-A-1 cells with the higher expres- sion levels of TFR was higher than that of the SK-MES-1 cells at the same concentration. The expres- sion of Caspase2, Caspase 9, Caspasel0 and Bax, p53 were up-regulated by GA along with the in- crease of GA concentration. Conclusion GA induces the apoptosis of SPC-A-1 and SK-M ES-1 ceils by binding TFR on the cell surface. Both endogenous and exogenous apoptosis pathways participated in the GA-induced lung cancer cell apoptosis. GA is a highly efficient anticancer drug with broad poten- tial. In clinical practice, the histopathological quantitation of TFR expression levels in tumor tissues may become a predictor of the sensitivity of patients＇ tumors to GA treatment.
出处
《实用临床医药杂志》
CAS
2013年第21期53-57,共5页
Journal of Clinical Medicine in Practice
