目的 研究雷公藤紅素對(duì)胃癌MFC細(xì)胞內(nèi)PI3K/AKT/mTOR信號(hào)通路的影響及其對(duì)胃癌MFC細(xì)胞增殖的抑制和促凋亡作用機(jī)制。方法 分別設(shè)置對(duì)照組和雷公藤紅素低、中、高劑量（5、10、20 mmol/L）組，采用MTT法檢測(cè)雷公藤紅素對(duì)胃癌MFC細(xì)胞增殖的影響；采用流式細(xì)胞技術(shù)檢測(cè)雷公藤紅素對(duì)胃癌MFC細(xì)胞周期的影響及MFC細(xì)胞凋亡的情況；Western blotting檢測(cè)雷公藤紅素對(duì)胃癌MFC細(xì)胞內(nèi)凋亡相關(guān)蛋白Bax、Bcl-2和PI3K、AKT和mTOR蛋白表達(dá)的影響；實(shí)時(shí)定量PCR檢測(cè)雷公藤紅素對(duì)胃癌MFC細(xì)胞內(nèi)PI3K、AKT和mTOR mRNA表達(dá)的影響。結(jié)果 與對(duì)照組比較，雷公藤紅素能夠呈劑量相關(guān)性地顯著抑制胃癌MFC細(xì)胞的增殖（P<0.05）；與對(duì)照組比較，雷公藤紅素能夠呈劑量相關(guān)性地顯著引起MFC細(xì)胞G₂/M期阻滯（P<0.05）；與對(duì)照組比較，雷公藤紅素能夠呈劑量相關(guān)性地顯著促進(jìn)MFC細(xì)胞的凋亡（P<0.05）；與對(duì)照組比較，雷公藤紅素能夠呈劑量相關(guān)性地顯著抑制MFC細(xì)胞內(nèi)抗凋亡蛋白Bcl-2蛋白和PI3K、AKT、mTOR蛋白的表達(dá)（P<0.05），顯著促進(jìn)MFC細(xì)胞內(nèi)促凋亡蛋白Bax的表達(dá)（P<0.05）；與對(duì)照組比較，雷公藤紅素能夠呈劑量相關(guān)性地顯著抑制MFC細(xì)胞內(nèi)PI3K、AKT和mTOR mRNA的表達(dá)（P<0.05）。結(jié)論 雷公藤紅素能夠抑制胃癌MFC細(xì)胞的增殖并促進(jìn)胃癌MFC細(xì)胞凋亡，其作用機(jī)制可能是通過(guò)抑制胃癌MFC細(xì)胞內(nèi)PI3K/AKT/mTOR信號(hào)通路中PI3K、AKT、mTOR等蛋白的表達(dá)而抑制胃癌MFC細(xì)胞的增殖，進(jìn)而促進(jìn)胃癌MFC細(xì)胞內(nèi)促凋亡蛋白Bax的表達(dá)，同時(shí)抑制抗凋亡蛋白Bcl-2的表達(dá)，從而促進(jìn)胃癌MFC細(xì)胞凋亡。

Objective To study the effect of tripterine on PI3K/AKT/mTOR signaling pathway in gastric cancer MFC cells and its mechanism of inhibiting proliferation and promoting apoptosis of gastric cancer MFC cells. Methods The control group, low dose medium dose, and high dose (5, 10, 20 mmol/L) groups were used to test the proliferation of gastric cancer MFC cells. MTT assay was used to detect the effects of tripterine on the proliferation of gastric cancer MFC cells. The effects of tripterine on the cell cycle of gastric cancer MFC cells and the apoptosis of MFC cells were detected by flow cytometry. The effects of tripterine on apoptosis-related proteins Bax, Bcl-2, and the expression of PI3K, AKT and mTOR proteins in gastric cancer MFC cells were studied by Western blotting. The effects of tripterine on the expression levels of PI3K, AKT and mTOR mRNA in gastric cancer MFC cells were detected by real-time quantitative PCR. Results Compared with the control group, tripterine could significantly inhibit the proliferation of gastric cancer MFC cells in a dose-dependent manner (P < 0.05). Compared with the control group, tripterine could significantly induce G₂/M phase arrest of MFC cells in a dose-dependent manner (P < 0.05). Compared with the control group, tripterine could significantly promote the apoptosis of MFC cells in a dose-dependent manner (P < 0.05). Compared with the control group, tripterine could significantly inhibit the expression of anti-apoptotic protein Bcl-2, and PI3K, AKT, and mTOR proteins in MFC cells in a dose-dependent manner (P < 0.05), but promote the expression of pro-apoptotic protein Bax in MFC cells in a dose-dependent manner (P < 0.05). Compared with the control group, tripterine could significantly inhibit the transcription of PI3K, AKT and mTOR mRNA in MFC cells in a dose-dependent manner (P < 0.05). Conclusion Tripterine can inhibit the proliferation of gastric cancer MFC cells and promote the apoptosis of gastric cancer MFC cells. The mechanism of action may be to inhibit the proliferation of gastric cancer MFC cells by inhibiting the expression of PI3K, AKT, mTOR and other proteins in PI3K/AKT/mTOR signaling pathway in gastric cancer MFC cells, and then promote the expression of apoptosis-promoting protein Bax in gastric cancer MFC cells. At the same time, it can inhibit the expression of anti-apoptotic protein Bcl-2 and promote the apoptosis of gastric cancer MFC cells.

R966

京津翼基礎(chǔ)研究合作專(zhuān)項(xiàng)項(xiàng)目（H2018201306）