梓醇通过调控肿瘤血管生成及能量代谢抑制肝癌生长

Catalpol inhibits the growth of liver cancer by regulating tumor angiogenesis and tumor metabolism

目的探讨梓醇对HepG2肝癌细胞增殖、侵袭、生长、血管生成和能量代谢的影响。方法细胞增殖实验研究梓醇对HepG2细胞体外增殖的影响;LDH试剂盒检测梓醇对HepG2细胞的毒性作用;构建人肝癌HepG2裸小鼠细胞移植瘤模型,研究梓醇对体内肝癌生长的影响;Transwell实验研究梓醇对HepG2细胞体外侵袭的影响;小管形成实验检测梓醇对HepG2细胞诱导的血管生成的影响;免疫组化研究梓醇对移植瘤中能量代谢关键指标单羧酸转运蛋白-1(monocarboxylate transporter-1,MCT-1)、单羧酸转运蛋白-4(monocarboxylate transporter-4,MCT-4)和葡萄糖转运蛋白1(Glucose transporter 1,GLUT1)蛋白表达的影响。结果在一定浓度范围内,梓醇能够抑制HepG2细胞的体外增殖及侵袭,且具有一定的浓度依赖性;LDH检测显示其在50μmol·L-1时对HepG2细胞表现出毒性作用;与对照组相比,梓醇能够显著抑制HepG2裸小鼠移植瘤的体内生长;HepG2细胞培养上清液能够显著刺激HUVEC细胞的小管形成,而梓醇能够在体外抑制HepG2细胞诱导的小管形成;梓醇能够抑制HepG2裸小鼠移植瘤组织中MCT-1,MCT4和GLUT1蛋白的表达。结论梓醇具有抑制肝癌细胞增殖、侵袭及生长的能力,其机制可能与抑制肝癌的血管生成及肿瘤能量代谢密切相关。

Objective To investigate the effect of catalpol on proliferation,invasion and tumor angiogenesis of HepG2 hepatic carcinoma and its potential molecular mechanisms.Methods MTS was used to test the effect of catalpol on proliferation of HepG2 cancer cells.The toxicity of catalpol on HepG2 cancer cells was measured by LDH detection kit.HepG2 liver cancer xenograft model was used to detect the effect of catalpol on tumor growth.The effect of catalpol on invasion ability of HepG2 cancer cells was examined by Transwell experiment.The effect of catalpol on tumor angiogenesis was determined by tube formation.Immunohistochemical was used to determine the effect of catalpol on expressions of monocarboxylate transporter-1(MCT-1),monocarboxylate transporter-1(MCT-4)and Glucose transporter 1(GLUT1).Results Compared to the control group,the proliferation and growth of HepG2 liver cancer cells were significant inhibited by catalpol in vitro and in vivo.Catalpol showed toxic effect on HepG2 cells in 50μM.Catalpol inhibited tumor cell-induced tube formation.Immunohistochemical showed that the expressions of MCT-1,MCT-4 and GLUT1 were significant decreased by treatment with catalpol.Conclusion Catalpol can inhibit the proliferation,invasion and growth of liver cancer,the potential mechanisms may be due to it can inhibit tumor angiogenesis and tumor metabolism.