微信公众号

官网二维码
中国癌症防治杂志

中国癌症防治杂志 ›› 2023, Vol. 15 ›› Issue (6): 615-622.doi: 10.3969/j.issn.1674-5671.2023.06.04

• 基础研究 • 上一篇    下一篇

蔓荆子黄素通过调控糖代谢重编程抑制肝癌细胞增殖

  

  1. 陕西中医药大学第二临床医学院；铜川职业技术学院孙思邈医学院； 陕西中医药大学第一临床医学院；空军军医大学唐都医院介入疼痛科；陕西中医药大学 第二附属医院科研科，基础医学院
  • 出版日期:2023-12-25 发布日期:2023-12-26
  • 通讯作者: 晁旭 E-mail：chaoxu2004@126.com
  • 基金资助:
    陕西省中医药“双链融合”中青年科研创新团队建设项目（2022?SLRH?LJ?010）；陕西省中医药管理局2021—2022年度科研立项课题（2021?ZZ?JC001）

Vitexicarpin inhibits the proliferation of liver cancer cells by regulating glucose metabolism reprogramming

  • Online:2023-12-25 Published:2023-12-26

PDF (PC)

289

赞

摘要： 目的 探讨蔓荆子黄素对肝癌细胞增殖的影响及其分子机制。方法 用不同浓度（0.5、1.0、2.0 μmol/L）的蔓荆子黄素处理肝癌细胞SNU⁃368、SNU⁃739及人肝永生化细胞THLE⁃2，采用MTS实验和克隆形成实验检测蔓荆子黄素对肝癌细胞生长的影响，同时选出蔓荆子黄素处理肝癌细胞的适宜浓度。用过表达HIF⁃1α慢病毒及其阴性对照慢病毒感染肝癌细胞SNU⁃368和SNU⁃739，同时用适宜浓度的蔓荆子黄素处理过表达HIF⁃1α的肝癌细胞，采用qRT⁃PCR和Western blot检测肝癌细胞中HIF⁃1α、C⁃MYC和P53的表达情况，通过葡萄糖摄取水平、乳酸生成水平、细胞外培养液pH值和细胞氧耗检测实验分析肝癌细胞糖酵解、氧化磷酸化的情况，采用MTS实验和克隆形成实验检测细胞的增殖情况。 结果 蔓荆子黄素可降低肝癌细胞SNU⁃368和SNU⁃739的增殖能力，且呈一定的剂量和时间依赖效应。1.0 μmol/L蔓荆子黄素处理肝癌细胞SNU⁃739和SNU⁃368后，可降低肝癌细胞中的葡萄糖摄取水平和乳酸生成水平（均P<0.01），提高细胞外培养液pH值和细胞氧耗率（均P<0.01），抑制肝癌细胞中HIF⁃1α的表达（均P<0.05）。过表达HIF⁃1α可促进肝癌细胞的糖酵解，抑制氧化磷酸化，增强肝癌细胞的增殖能力（均P<0.05），而蔓荆子黄素可以逆转过表达HIF⁃1α对肝癌细胞增殖的促进作用（均P<0.05）。结论 蔓荆子黄素可通过抑制HIF⁃1α的表达抑制细胞糖酵解和促进氧化磷酸化，进而抑制肝癌细胞增殖。

关键词: 肝癌, 蔓荆子黄素, HIF?1α, 增殖, 糖代谢重编程

Abstract: Objective To investigate the effects of Vitexicarpin on the proliferation of liver cancer cells and its molecular mechanisms. Methods MTS assay and clonogenic formation assay were used to detect the effects of different concentrations of Vitexicarpin (0.5, 1.0 and 2.0 μmol/L, respectively) on the growth of liver cancer cell lines SNU⁃368 and SNU⁃739, as well as human liver immortalized cells THLE⁃2, the appropriate concentration of Vitexicarpin in treatment of liver cancer cells was selected at the same time. Liver cancer cell lines SNU⁃368 and SNU⁃739 were infected with HIF⁃1α overexpressing lentivirus and its negative control lentivirus, while the liver cancer cells overexpressing HIF⁃1α were treated with the appropriate concentration of Vitexicarpin. The expressions of HIF⁃1α, C⁃MYC, and P53 in liver cancer cell lines were detected by qRT⁃PCR and Western blot. The conditions of glycolysis and oxidative phosphorylation in liver cancer cells were analyzed by glucose uptake level, lactate production level, extracellular pH, and cellular oxygen consumption test. The proliferation of the cells was detected by MTS assay and clone formation assay. Results The proliferation of SNU⁃368 and SNU⁃739 cells was inhibited by Vitexicarpin with a dose and time dependent manner. After treatment with 1.0 μmol/L Vitexicarpin, the value of glucose uptake and lactate production in SNU⁃368 and SNU⁃739 liver cancer cells were reduced (all P<0.01), while the extracellular pH and cellular oxygen consumption rate were increased (all P<0.01), and the expression of HIF⁃1α was inhibited (P<0.05). Overexpression of HIF⁃1α could promote the glycolysis of liver cancer cells, inhibit oxidative phosphorylation, and enhance cell proliferation (all P<0.05), while the Vitexicarpin could reverse the growth⁃promoting effect of HIF⁃1α overexpression in liver cancer cells (all P<0.05). Conclusions Vitexicarpin can inhibit the proliferation of cell glycolysis and enhance oxidative phosphorylation by inhibiting the expression of HIF⁃1α, thereby inhibiting the proliferation of liver cancer cells.

Key words: Liver cancer cell；Vitexicarpin；HIF?1α；Proliferation；Reprogramming of glucose metabolism ,

中图分类号: 

  • R735.7