目的 考察2-脫氧葡萄糖（2-DG）聯(lián)合二甲雙胍（Met）協(xié)同抗人肝癌HepG2細胞作用并探索其機制。方法 刃天青法測定2-DG及Met單獨及聯(lián)合應用對HepG2細胞的生長抑制作用，利用金氏公式計算聯(lián)合用藥Q值；利用高內涵細胞成像系統(tǒng)考察單獨及聯(lián)合用藥對細胞線粒體膜電位及活性氧產(chǎn)生的影響；Western blotting檢測Cleave-Caspase 3、p-AMPK及p-mTOR的蛋白變化；考察AMPK及mTOR抑制劑對聯(lián)合用藥后細胞生長抑制作用的影響。結果 2-DG、Met單獨應用的IC₅₀值分別為2.45及16.35 mmol/L，聯(lián)合用藥對細胞生長抑制具有協(xié)同作用，Q值均大于1.15；聯(lián)合用藥能顯著降低細胞內線粒體膜電位及p-mTOR蛋白表達，顯著增加細胞內活性氧產(chǎn)生及Cleave-Caspase3、p-AMPK蛋白表達；抑制AMPK或mTOR能顯著增加聯(lián)合用藥對細胞的生長抑制作用（P<0.05、0.01）。結論 2-DG聯(lián)合Met具有協(xié)同抑制HepG2細胞增殖作用，其機制與降低細胞線粒體膜電位，促進活性氧產(chǎn)生、細胞凋亡，以及非AMPK依賴性的抑制mTOR活化有關。

Objective To investigate whether 2-deoxyglucose (2-DG) combined with metformin (Met) has synergistic antitumor effect on HepG2 cells, and explore the underling mechanisms. Methods The cell growth inhibitory ratio of HepG2 cells treated by 2-DG, Met, and the combination was determined by the resin azure method, and the synergistic antitumor effects of the combined application was also examined by calculating the Q values of Jin's formula; Mitochondrial membrane potential and reactive oxygen species generation were detected by high conformation cell imaging system; The expression level of Cleave-Caspase 3, p-AMPK, and p-mTOR were examined by Western blotting; The cell growth inhibitory ratio was detected by the resin azure method after AMPK and mTOR inhibitors administrating. Results The IC₅₀ values of 2-DG and Met alone in HepG2 cells were 2.45 mmol/L and 16.35 mmol/L, respectively. Combined application has synergistic antitumor effects, and the Q values of Jin's formula was more than 1.15. Combined application significantly reduced mitochondrial membrane potential and increased intracellular reactive oxygen species production and Cleave-Caspase3 expression. Combined application significantly increased the expression of P-AMPK, decreased the expression of p-mTOR. Moreover, inhibiting AMPK and mTOR by the inhibitors significantly enhanced the cell growth inhibitory effect of combination group (P<0.05 and 0.01). Conclusion 2-DG combined with Met has synergistic antitumor effect on HepG2 cells. The underlying mechanism is related to decreasing mitochondrial membrane potential, promoting reactive oxygen production and apoptosis, and non-AMPK dependent inhibition of mTOR activation.