摘要
通过体外和体内模型研究光甘草定对小鼠黑色素瘤B16F10细胞增殖的抑制作用及其分子机制。B16F10细胞经光甘草定处理后可抑制其增殖,且具有浓度依赖性;诱导B16F10细胞凋亡,观察到明显的细胞凋亡状态,细胞内凋亡相关基因及蛋白Bax表达显著上升,Bcl-2则表达下调。进一步的研究发现,经光甘草定处理后的B16F10细胞中,培养基中葡萄糖含量升高,而ATP含量、乳酸生成均降低;细胞内糖酵解相关基因及蛋白HK2、Ldha表达下调。同时,经光甘草定处理后,移植瘤小鼠的肿瘤组织生长受到明显抑制,肿瘤组织内细胞凋亡率显著升高,Bax表达明显上升,而Bcl-2、HK2和Ldha则表达均下调。说明,光甘草定在一定浓度范围内抑制了小鼠黑色素瘤B16F10细胞的增殖,诱导细胞凋亡,而其诱导细胞凋亡的机制可能与调控糖酵解相关基因的表达相关。
To explore the molecular mechanism of glabridin-induced B16F10 cell proliferation inhibition via in vitro and in vivo model of melanoma. Glabridin induced B16F10 cell proliferation inhibition and cell apoptosis in a dose-dependent manner. The Bax mRNA and protein expressions were up-regulated and the Bcl-2 was down-regulated in glabridin-treated B16F10 cells. Further studies showed that glabridin decreased the production of ATP and lactic acid in mouse melanoma B16F10 cells. Glabridin down-regulated the mRNA and protein expressions of glycolysis-related kinase genes （Hk2 and Ldha） in B16F10 cells. In addition,the animal model of mouse melanoma indicated that glabridin treatment suppressed tumor growth and induced tumor apoptosis. Both the mRNA and protein levels of glycolysis-related kinase genes（ Hk2 and Ldha） and Bcl-2 in tumor tissue were also decreased and Bax was increased in glabridin treated mice. It was concluded thatglabridin inhibited the proliferation and induced apoptosis of melanoma B16F10 cells in a dose-dependent manner, and the inhibition of glycolysis played a crucial role in the induction of apoptosis in glabridin-treated B16F10 cells.
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2017年第5期836-842,共7页
Natural Product Research and Development
基金
滨州医学院科研启动基金(BY2014KYQD01)
国家自然科学基金(31471338)
山东省高等学校优势学科人才团队培育计划
