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目的:观察二氢丹参酮(DHT)对胃癌细胞MGC803增殖、迁移和凋亡能力的影响,并探讨其作用的分子机制。方法:利用不同浓度的DHT处理细胞后,MTT检测细胞增殖能力,细胞划痕实验观察细胞运动能力,Annexin V-FITC/PI检测细胞凋亡率,定量PCR和Western blot检测胃癌凋亡和迁移相关基因的表达情况。结果:与空白对照组比较,DHT可显著抑制MGC803细胞的体外增殖能力,降低细胞的迁移能力,诱导MGC803细胞发生凋亡,且呈现剂量依赖性。定量PCR实验结果表明,DHT可显著抑制MGC803细胞中MMP2、MMP9 m RNA的表达(P<0.05,P<0.01),降低抗凋亡蛋白Bcl-2的表达水平,显著提高促凋亡蛋白PUMA的水平(P<0.01)。DHT加入后可抑制STAT3的磷酸化水平,提高Fox O3信号通路的活性,增加抑癌基因p53的蛋白表达,降低Gli1 m RNA表达(P<0.01),并提高HHIP m RNA表达水平(P<0.01)。结论:DHT能够抑制胃癌细胞MGC803的增殖和迁移能力,诱导细胞凋亡,其机制可能与MMP2、MMP9蛋白的表达降低、Hedgehog通路活性抑制和凋亡调控基因PUMA、STAT3、Fox O3和p53的表达水平改变有关。
Objective: To observe the effect of DHT on the proliferation, migration and apoptosis of gastric cancer cell line MGC803 and to explore its molecular mechanism. Methods: After treated with different concentrations of DHT, MTT assay was used to detect cell proliferation, cell scratch assay to observe cell motility, Annexin V-FITC / PI to detect cell apoptosis rate, quantitative PCR and Western blot to detect apoptosis and migration of gastric cancer Gene expression. Results: Compared with the blank control group, DHT could significantly inhibit the proliferation of MGC803 cells in vitro, reduce the migration ability of cells and induce the apoptosis of MGC803 cells in a dose-dependent manner. Quantitative PCR results showed that DHT significantly inhibited the expression of MMP2 and MMP9 mRNA in MGC803 cells (P <0.05, P <0.01), decreased the expression of anti-apoptotic protein Bcl-2 and significantly increased the expression of PUMA Level (P <0.01). DHT could inhibit the phosphorylation of STAT3, increase the activity of FoxO3 signal pathway, increase the protein expression of tumor suppressor gene p53, decrease the expression of Gli1 m RNA (P <0.01), and increase the expression level of HHIP m RNA (P <0.01) ). CONCLUSION: DHT can inhibit the proliferation and migration of MGC803 cells and induce the apoptosis of gastric cancer cells. The mechanism may be related to the decrease of MMP2 and MMP9, the inhibition of Hedgehog pathway and the expression of PUMA, STAT3, FoxO3 and p53 The level of change related.