辛伐他汀通过AMPK/mTOR信号通路及氧化应激对鼻咽癌细胞凋亡和侵袭转移的作用研究

目的：研究辛伐他汀对体外人鼻咽癌细胞CNE-2增殖抑制、细胞凋亡及侵袭转移的影响,并对其潜在作用机制进行研究探讨。方法：采用MTT实验测不同浓度梯度辛伐他汀(0、0.1、1、10mmol/L)对CNE-2细胞增殖抑制作用；细胞凋亡情况的检测采用流式细胞术,Transwell实验检验细胞侵袭迁移能力,Western blot检测细胞中Bax、Bcl-2、AMPK、pAMPK、mTOR蛋白表达水平,检测分析丙二醛量(MDA)和超氧化物歧化酶(SOD)活性的前后变化。结果：与对照组相比,辛伐他汀对CNE-2细胞的增殖抑制率明显升高,凋亡率明显升高,且侵袭转移能力明显降低,具有明显的剂量和时间依赖关系,差异均具有统计学意义(P<0.05), 此外,与对照组相比,辛伐他汀能够显著增强Caspase-3的活性, 使得AMPK/pAMPK/Bax蛋白表达增加,mTOR/Bcl-2蛋白表达下降,差异具有统计学意义(P<0.05)。辛伐他汀能够增加MDA含量,减少SOD活性,以上作用均具有剂量依赖性,差异具有统计学意义(P<0.05)。结论：辛伐他汀对鼻咽癌细胞增殖抑制、诱导细胞凋亡和抑制侵袭转移的作用,可能与AMPK/mTOR通路及氧化应激有关。

Effects of simvastatin on cell proliferation, apoptosis, migration and invasion in CNE-2 nasopharyngeal carcinoma cells and its mechanisms

Objective To investigate the effects of simvastatin on cell proliferation, apoptosis, migration and invasion in nasopharyngeal carcinoma cells CNE-2 and its mechanisms. Methods MTT analysis was used to measure the inhibitory effect of simvastatin with different doses (0, 0.1, 1 and 10.0mmol/L) on CNE-2 cells. Flow cytometry was performed to analyze cell cycle andScell apoptosis. Transwell experiment was used to detect the cell migration and invasion. Western Blot was used to evaluate the expressions of Bax, Bcl-2, AMPK, pAMPK and mTOR. The level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the CNE-2 cells were also examined.Results The inhibitory rate and apoptosis rate of simvastatin on CNE-2 nasopharyngeal carcinoma cells were higher than that in control group (P<0.05)Sand the cell proliferation inhibitionSrate and apoptosis rate showed a dose-andStime-dependent manner. The cell migration and invasion ability was decreased significantly in the simvastatin group(P<0.05). Compared with the control group, the activity of Caspase-3 in CNE-2 cells was increased significantly, and the expression levels of AMPK, pAMPK and Bax were increased significantly while the expression of mTOR and Bcl-2 were decreased significantly (P<0.05). The content rations of MDA increased significantly (P < 0.05) , and SOD decreased (P<0.05) by simvastatin. All the aboveSeffects of simvastatin were dose-dependent and the differencesSwere statistically significant (P<0.05). Conclusions Simvastatin may inhibit nasopharyngeal carcinoma cell proliferation, migration, and invasion and promote its apoptosis,and the effects may related with AMPK/mTOR signaling pathways and oxidative stress.