P53蛋白参与灵芝酸抑制癌细胞增殖的过程

Inhibition of ganoderic acid mediated by P53 protein on cancer cells proliferation

通过对灵芝三萜类物质(灵芝酸T)抑制肺癌H1299(p53-/-)细胞、肺癌95-D(p53+/+)细胞增殖实验,考察了P53蛋白对灵芝酸抑制增殖作用的影响。结果表明:通过比较IC50,表达野生型P53蛋白的95-D细胞比不表达P53蛋白的H1299细胞对灵芝酸T的敏感性高3.3倍。P53抑制剂Pifithrin-α与灵芝酸T联合处理能显著地降低灵芝酸T对95-D细胞增殖的抑制率(p<0.05)。进一步研究表明灵芝酸T可诱导95-D(p53+/+)中P53蛋白表达,并促进细胞凋亡。以上结果提示P53蛋白参与了灵芝酸T抑制肿瘤细胞增殖的过程,可能是灵芝三萜类物质抗肿瘤的作用靶点。本研究可为开发辅助抑制肿瘤类保健食品研究提供理论基础。

The roles of P53 protein in the inhibitory effect of ganoderic acid T(GA-T)on human lung cancer cells proliferation were evaluated by H1299( p53 ^-/- ) and 95-D( p53^+/+) cells.The results showed that 95-D cell which expressed P53 protein was more sensitive to the GA-T than H1299 cell which unexpressed P53 protein. The cytotoxicity of GA-T on 95-D cells was 3.3 times higher than that of H1299 cell significantly.The cytotoxicity of GA-T on 95 - D cancer cells decreased significantly after pifithrin- α treatment ( p < 0.05 ). Furthermore, GA- T stimulated the expression of P53 in 95-D cancer cells and induced the apoptosis of 95-D cancer cells dose- dependently.The results mentioned above proved that P53 participated in the process of anti-proliferation of cancer cell by GA-T and should be a potent target of ganoderic acids.The results in this paper should provide the theoretical foundation for development of functional food.