植物乳杆菌CGMCC8198干预脂代谢紊乱发挥肝癌防治作用

Lactobacillus plantarum CGMCC8198 exerts prevention and treatment of liver cancer effects by intervening in lipid metabolism disorders

摘要:

[背景] 脂代谢异常是肝癌发生发展过程中重要的代谢事件，研究发现多种乳酸菌在调节糖脂代谢过程中发挥重要作用。[目的] 探究植物乳杆菌CGMCC8198是否会通过调节HMGCR/SMYD3脂代谢通路，进而对肝癌细胞的发生发展产生影响。[方法] 采用不同浓度的（5、10、15 μg/mL）植物乳杆菌CGMCC8198破碎上清液（Lactobacillus plantarum CGMCC 8198 Crushed Supernatant，LpS）处理HepG2细胞不同时间。利用蛋白免疫印迹（Western Blot）、油红染色以及实时定量荧光PCR （Real Time Quantitative PCR，RT-qPCR）等方法检测LpS对肝癌细胞脂肪变性及HMGCR/SMYD3脂代谢关键通路的影响；通过MTT法、细胞划痕实验、流式细胞术检测LpS对脂代谢紊乱过程中HepG2细胞增殖、迁移和凋亡的影响。[结果] LpS可以抑制脂代谢紊乱肝癌细胞中HMGCR、SMYD3、SREBP-2等基因的表达，同时也可以剂量依赖地抑制细胞增殖、迁移，促进细胞凋亡。[结论] LpS可以通过抑制脂代谢关键转录调控因子SREBP-2和HMGCR的表达来抑制肝癌细胞的脂代谢，进而促进肝癌细胞的内源性凋亡。

关键词:植物乳杆菌;肝癌;细胞增殖;细胞迁移;细胞凋亡

Abstract:

[Background] Abnormal lipid metabolism is an important metabolic event in the development of liver cancer. Role of lactic acid bacteria in regulating glucose and lipid metabolism has been widely reported. [Objective] To investigate whether Lactobacillus plantarum CGMCC8198 could regulate the HMGCR/SMYD3 lipid metabolism pathway, thereby affecting the occurrence and development of liver cancer cells. [Methods] HepG2 cells were treated with different concentrations (5, 10, 15 μg/mL) of Lactobacillus plantarum CGMCC8198 crushed supernatant (LpS) for different times. Western Blot, oil red staining and real-time quantitative PCR (RT-qPCR) were used to detect the effects of LpS on fatty degeneration of liver cancer cells and the key pathway of HMGCR/SMYD3 lipid metabolism; MTT, cell scratch test and flow cytometry were used to detect the effect of LpS on the proliferation, migration and apoptosis of HepG2 cells in the process of lipid metabolism disorders. [Results] The expression of key lipid metabolism genes such as HMGCR, SMYD3, SREBP-2 could be inhibited by LpS in lipid metabolism disorders liver cancer cells, while the proliferation and migration could be inhibited and the cell apoptosis could be promoted of liver cells in the process of lipid metabolism disorders. [Conclusion] LpS could inhibit the lipid metabolism of liver cancer cells by inhibiting the expression of key transcriptional regulators of lipid metabolism SREBP-2 and HMGCR, thereby promoting endogenous apoptosis of liver cancer cells.

Key words:Lactobacillus plantarum;liver cancer;cell proliferation;cell migration;cell apoptosis