期刊文献+

α-Hederin inhibits growth of lung cancer A549 cells in vitro and in vivo by decreasing c-Myc and HIF-1α dependent glycolysis

α-Hederin inhibits growth of lung cancer A549 cells in vitro and in vivo by decreasing c-Myc and HIF-1α dependent glycolysis
下载PDF
导出
摘要 OBJECTIVEα-Hederin is an effective component of the traditional Chinese medicine Pulsatilla chinensis,which has been reported to exert many pharmacological activities.However,the effect ofα-hederin on metabolism is still unclear.This study aimed to illuminate the role ofα-hederin in glucose metabolism in lung cancer cells and investigate the molecular mechanism ofα-hederin.METHODS CCK8 and colony formation assays were employed to assess the anti-proliferative effects induced byα-hederin.Glucose uptake,ATP generation,and reduced lactate production were measured using kits,and an A549 tumor xenograft mouse model of lung cancer was used to assess the in vivo antitumor effect ofα-hederin(5,10 mg·kg^-1).Glycolytic-related key enzymes were detected by Western blotting and immunohisto⁃chemical staining.RESULTS Cell proliferation was significantly inhibited byα-hederin in a dose-dependent manner and thatα-hederin inhibited glucose uptake and ATP generation and reduced lactate production.Furthermore,α-hederin remarkably inhibited hexokinase 2(HK2),glucose transporters 1(GLUT1),pyruvate kinase M2(PKM2),lactate dehydro⁃genase A(LDHA),monocarboxylate transporter(MCT4),c-Myc,and hypoxia inducible factor-1α(HIF-1α)protein expres⁃sion.Using inhibitors,we proved thatα-hederin inhibits glycolysis by inhibiting glycolytic regulators.Moreover,a tumor xenograft mouse model of lung cancer further confirmed thatα-hederin inhibits lung cancer growth via inhibiting glycolysis in vivo.CONCLUSIONα-Hederin inhibits the growth of non-small cell lung cancer A549 cells by inhibiting glycolysis.The mechanism of glycolysis inhibition includesα-hederin inhibiting the expression of the glycolytic regulatory factors HIF-1α and c-Myc. OBJECTIVE α-Hederin is an effective component of the traditional Chinese medicine Pulsatilla chinensis,which has been reported to exert many pharmacological activities. However, the effect of α-hederin on metabolism is still unclear. This study aimed to illuminate the role of α-hederin in glucose metabolism in lung cancer cells and investigate the molecular mechanism of α-hederin. METHODS CCK8 and colony formation assays were employed to assess the anti-proliferative effects induced by α-hederin. Glucose uptake, ATP generation, and reduced lactate production were measured using kits, and an A549 tumor xenograft mouse model of lung cancer was used to assess the in vivo antitumor effect of α-hederin(5, 10 mg·kg-1). Glycolytic-related key enzymes were detected by Western blotting and immunohistochemical staining. RESULTS Cell proliferation was significantly inhibited by α-hederin in a dose-dependent manner and that α-hederin inhibited glucose uptake and ATP generation and reduced lactate production. Furthermore, α-hederin remarkably inhibited hexokinase 2(HK2), glucose transporters 1(GLUT1), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), monocarboxylate transporter(MCT4), c-Myc, and hypoxia inducible factor-1α(HIF-1α) protein expression. Using inhibitors, we proved that α-hederin inhibits glycolysis by inhibiting glycolytic regulators. Moreover, a tumor xenograft mouse model of lung cancer further confirmed that α-hederin inhibits lung cancer growth via inhibiting glycolysisin vivo. CONCLUSION α-Hederin inhibits the growth of non-small cell lung cancer A549 cells by inhibiting glycolysis.The mechanism of glycolysis inhibition includes α-hederin inhibiting the expression of the glycolytic regulatory factors HIF-1α and c-Myc.
出处 《中国药理学与毒理学杂志》 CAS 北大核心 2019年第9期682-683,共2页 Chinese Journal of Pharmacology and Toxicology
基金 National Natural Science Foundation of China(81460618 81860720 81660683) Scientific Foundation of Double World-classes Subject Development of Jiangxi University of TCM(JXSYLXK-ZHYAO124)
关键词 α-hederin lung cancer GLYCOLYSIS C-MYC hypoxia inducible factor-1α α-hederin lung cancer glycolysis c-Myc hypoxia inducible factor-1α
  • 相关文献

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部