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目的探讨左卡尼汀对氟尿嘧啶(5-fluorouracil,5-Fu)抑制人胃腺癌MGC803细胞增殖作用的影响。方法将MGC803细胞分为阴性对照组、5-Fu组、左卡尼汀和5-Fu联合用药组(左卡尼汀+/→5-Fu)进行实验。四甲基偶氮唑蓝(MTT)法检测细胞的增殖,流式细胞术检测细胞凋亡和细胞周期,蛋白质印迹法检测Bcl-2、Bax、ANT1和cleaved-PARP蛋白的表达。结果与5-Fu单药组相比,左卡尼汀和5-Fu联合用药组抑制MGC803细胞增殖的作用增强,细胞凋亡百分率增大,细胞周期S期阻滞,上调Bax、ANT1和cleaved-PARP蛋白的表达,下调Bcl-2蛋白的表达。实验结果还显示,左卡尼汀和5-Fu联合应用时,给药方法可以影响5-Fu对MGC803细胞的抑制作用。与左卡尼汀+5-Fu组相比,左卡尼汀→5-Fu组细胞凋亡百分率由(19.60±1.06)%增加至(24.17±3.12)%(P<0.05),G0/G1期细胞比例由(72.95±0.91)%降低至(62.62±1.04)%,S期细胞比例由(27.05±0.91)%增加至(37.35±1.03)%(P<0.001)。结论左卡尼汀可能通过影响Bcl-2家族蛋白的表达和细胞周期,增强5-Fu对MGC803细胞增殖的抑制作用。
Objective To investigate the effects of levocarnitine on the proliferation of human gastric adenocarcinoma MGC803 cells induced by 5-fluorouracil (5-Fu). Methods MGC803 cells were divided into negative control group, 5-Fu group, levocarnitine and 5-Fu combined group (levocarnitine + / → 5-Fu) for experiments. Cell proliferation was detected by MTT assay. Apoptosis and cell cycle were detected by flow cytometry. The protein expressions of Bcl-2, Bax, ANT1 and cleaved-PARP were detected by Western blotting. Results Compared with 5-Fu monotherapy group, L-carnitine and 5-Fu combined treatment group inhibited the proliferation of MGC803 cells, the percentage of apoptosis increased, cell cycle S phase arrest, up-regulated Bax, ANT1 and cleaved -PARP protein expression, down-regulate Bcl-2 protein expression. The experimental results also show that when L-carnitine and 5-Fu are used in combination, the administration method can affect the inhibitory effect of 5-Fu on MGC803 cells. Compared with levocarnitine + 5-Fu group, the percentage of apoptosis in L-carnitine → 5-Fu group increased from (19.60 ± 1.06)% to (24.17 ± 3.12)% The percentage of senescent cells decreased from (72.95 ± 0.91)% to (62.62 ± 1.04)%, and the percentage of S phase cells increased from (27.05 ± 0.91)% to (37.35 ± 1.03)% (P <0.001). Conclusion L-carnitine may enhance the inhibitory effect of 5-Fu on the proliferation of MGC803 cells by affecting the expression of Bcl-2 family proteins and cell cycle.