RhoGDI2与PI3K/Akt/mTOR信号通路在肺癌细胞中的相关性研究

目的探讨肿瘤转移相关因子RhoGDI2与PI3K/Akt/mTOR信号通路在肺癌侵袭转移过程中的作用及相关机制。方法利用PI3K/Akt/mTOR信号通路上特异性的抑制剂,采用MTT法,伤口愈合实验及侵袭实验观察不同浓度药物对肺癌95D细胞生长侵袭转移能力的影响,通过Western Blot方法观察RhoGDI2蛋白水平的变化。结果PI3K抑制剂LY294002及mTOR抑制剂Rapamycin都能抑制肺癌细胞95D的侵袭转移能力,联合应用抑制作用更强。PI3K抑制剂LY294002处理组RhoGDI2蛋白的表达量增加,且随浓度增加RhoGDI2蛋白表达也增加。mTOR抑制剂Rapamycin组,在低浓度时增加RhoGDI2蛋白的表达,但增大Rapamycin的浓度,RhoGDI2蛋白的表达反而降低。低浓度LY294002组和Rapa-mycin组联合应用可以明显增加RhoGDI2蛋白的表达。结论PI3K/Akt/mTOR信号通路中Akt的活化与RhoGDI2密切相关,RhoGDI2可能直接或间接通过与Akt的相互作用参与调节肺癌的侵袭转移的过程。

Relationship between RhoGDI2 and PI3K/Akt/mTOR signalling pathway in lung cancer cells

Objective To investigate the effects of RhoGDI2 and PI3K/Akt/mTOR on invasion and metastasis of lung cancer,and the possible interplay between PI3K/Akt/mTOR pathway and RhoGDI2 signalling in 95D lung cancer cells.Methods Effects of PI3K/Akt/mTOR antagonists on 95D lung cancer cell growth,mobility and invasion were measured by MTT assay,wound healing assay and cell invasion assay.The expression of RhoGDI2 protein was detected by Western blot.Results Either or both PI3K/Akt/mTOR antagonists inhibited 95D lung cancer cell growth,invasion and metastasis.The expression of RhoGDI2 protein was decreased in the 30 ng/ml rhHGF group,while it was increased in LY294002 groups and Rapamycin 10nmol/l and 20 nmol/l groups.The expression of RhoGDI2 protein was decreased in the Rapamycin 40nmol/l group.Combination of LY294002 and Rapamycin increased RhoGDI2 expression significantly.Conclusion RhoGDI2 has a close relationship with the activation of Akt by the PI3K/Akt/mTOR signalling pathway.RhoGDI2 may be directly or indirectly involvd in the invasion and metastasis of lung cancer by its interaction with Akt.