目的 研究吉馬酮誘導肺癌 A549、 鼻咽癌 CNE-1、 肝癌 HepG2 細胞凋亡的機制 。 方法 50、 150、 200、250、300 μmol·L^-1的吉馬酮處理肝癌 HepG2、肺癌 A549、鼻咽癌 CNE-1、結(jié)腸癌 Caco-2 細胞 24、48、72 h 后，MTT 實驗檢測細胞的存活率的變化。100、150、200 μmol·L^-1的吉馬酮分別處理 A549、HepG2、CNE-1細胞 48 h后采用流式細胞術(shù)檢測細胞凋亡的變化；Western blotting 實驗檢測細胞凋亡標志蛋白 cleaved-Caspase-3、Caspase-3 的變化，檢測乙型肝炎 X相互作用蛋白（HBXIP）、p53蛋白的表達量變化。分別在 A549、HepG2、CNE-1細胞中應用 siRNA 敲低 HBXIP，Westernblotting實驗檢測 HBXIP的敲低效果及 p53蛋白表達變化；MTT實驗檢測敲低 HBXIP對吉馬酮誘導的細胞增殖抑制作用的影響。結(jié)果 吉馬酮對鼻咽癌CNE-1、肝癌HepG2細胞增殖抑制作用較強，與溶劑對照組比較，200、250、300 μmol·L^-1組細胞存活率顯著下降（P＜0.05）；在高濃度時對肺癌A549細胞增殖抑制效果較強，與溶劑對照組比較，250、300 μmol·L^-1組細胞存活率顯著下降（P＜0.05）；對結(jié)腸癌Caco-2細胞作用相對較弱。與對照組比較，100、150、200 μmol·L^-1吉馬酮處理A549、HepG2、CNE-1細胞 48 h后，凋亡率顯著升高（P＜0.05），cleaved-Caspase-3、p53蛋白表達顯著上升（P＜0.05）；以 150、200 μmol·L^-1吉馬酮處理A549、HepG2、CNE-1細胞48 h后，HBXIP的蛋白表達顯著降低（P＜0.05）。siRNA-HBXIP處理48 h后，與對照組比較，HBXIP的蛋白表達量顯著下降（P＜0.05），p53蛋白表達量顯著上升（P＜0.05）。與單獨使用的相同濃度的吉馬酮相比，沉默HBXIP后A549、HepG2、CNE-1細胞對吉馬酮的敏感度明顯提高，150、200、250 μmol·L^-1組均差異顯著（P＜0.05）。結(jié)論 吉馬酮可以抑制A549、HepG2、CNE-1細胞增殖、誘導細胞凋亡，作用機制可能與調(diào)控HBXIP/p53信號通路相關。

Objective Study the mechanism of gemmazone induced apoptosis in A549, CNE-1, and HepG2 cells.Methods After 50, 150, 200, 250, and 300 μmol·L^-1 germacrone treated in HepG2, A549, CNE-1, and Caco-2 cells for 24, 48 and 72 h, the MTT assay was preformed to detect the changes of cell viability. When 100, 150 and 200 μmol·L^-1 germacrone treated in A549, HepG2 and CNE-1 cells for 48 h, the changes of cell apoptosis were detected by flow cytometry, and the Western blotting was used to detect the changes of cleaved-Caspase 3, Caspase-3 HBXIP, and P53 proteins. The expressions of HBXIP and P53 were detected by Western blotting after HBXIP knocked down in A549, HepG2 and CNE-1 cells. The effect of knockdown of HBXIP on the inhibitory proliferation induced by germacrone was detected by MTT assay.Results Gemmazone had a strong inhibitory effect on the proliferation of nasopharyngeal carcinoma CNE-1 and liver cancer HepG2 cells, compared with the solvent control group, the cell survival rate of the 200, 250, and 300 μmol·L^-1 group significantly decreased (P < 0.05). At high concentrations, the inhibitory effect on the proliferation of lung cancer A549 cells was better, compared with the solvent control group, the cell survival rate of the 250, 300 μmol·L^-1 group significantly decreased (P < 0.05). The effect on colon cancer Caco-2 cells was relatively weak. Compared with the control group, after 48 hours of treatment with 100, 150, 200 μmol·L^-1 gemmazone, the apoptosis rate of A549, HepG2, and CNE-1 cells significantly increased (P < 0.05), and the expression of cleaved-Caspase-3 and p53 proteins significantly increased (P < 0.05). After 48 hours of treatment with 150, 200 μmol·L^-1 gemmazone in A549, HepG2, and CNE-1 cells, the protein expression of HBXIP was significantly reduced (P < 0.05). After 48 hours of siRNA-HBXIP treatment, compared with the control group, the protein expression of HBXIP significantly decreased (P < 0.05) and the expression of p53 protein significantly increased (P < 0.05). Compared with the same concentration of gemmazone used alone, silencing HBXIP significantly increased the sensitivity of A549, HepG2, and CNE-1 cells to gemmazone, with values of 150, 200, and 250 μmol·L^-1 group showed significant differences (P < 0.05).Conclusion Gematone can inhibit the proliferation of A549, HepG2, and CNE-1 cells and induce cell apoptosis, and the mechanism of action may be related to the regulation of the HBXIP/p53 signaling pathway.

R285.5

合肥市自然科學基金（2021012）；安徽省高等學校科學研究項目（自然科學類）（2022AH050712）；合肥市第二人民醫(yī)院院級課題（2021ygkt35）