白藜芦醇通过抑制HMGB1调控卵巢癌细胞凋亡的机制研究  

Mechanism of resveratrol regulating ovarian cancer cell apoptosis by inhibiting HMGB1

作　　者：吕红青 张琳[1] Lyu Hongqing;Zhang Lin(Department of Gynaecology,Jinhua Municipal Central Hospital,Jinhua 321000,China)

机构地区：[1]金华市中心医院妇科,金华321000

出　　处：《中华内分泌外科杂志》2023年第1期100-105,共6页Chinese Journal of Endocrine Surgery

基　　金：金华市科技计划项目(2020-4-019)。

摘　　要：目的探讨白藜芦醇对卵巢癌细胞凋亡的影响及其分子机制,为治疗卵巢癌寻找潜在的新靶点。方法将卵巢癌SKOV-3细胞分为对照组和白藜芦醇组。用MTT法检测白藜芦醇处理后卵巢癌SKOV-3细胞的活力。白藜芦醇干预SKOV-3细胞24 h后,Western blot检测Bcl-2、Bax、Caspase-3、HMGB1、TLR4和NF-ĸB的表达情况。将si-NC、si-HMGB1、Rb1+pcDNA3.1或Rb1+pcDNA3.1-HMGB1转染卵巢癌SKOV-3细胞,MTT法检测细胞对白藜芦醇敏感性的变化。白藜芦醇处理转染细胞,流式细胞术检测细胞凋亡的变化。结果白藜芦醇能抑制卵巢癌SKOV-3细胞生长,且白藜芦醇浓度越高抑制效果越显著。对照细胞和实验组细胞HMGB1表达量分别为1.24±0.15和0.86±0.11,25μM白藜芦醇能抑制HMGB1的蛋白水平;HMGB1下调后对白藜芦醇的敏感性增加,且促进SKOV-3细胞凋亡;HMGB1过表达后对白藜芦醇的抗性增加,且抑制SKOV-3细胞凋亡。对照组和白藜芦醇组TLR4表达量分别为0.98±0.12和0.63±0.08,NF-ĸB表达量分别为1.21±0.14和0.45±0.07,25μM白藜芦醇能下调TLR4、NF-ĸB的蛋白水平。结论白藜芦醇可促进卵巢癌SKOV-3细胞凋亡,该机制可能与下调HMGB1/TLR4/NF-ĸB通路相关,为白藜芦醇治疗卵巢癌提供了基础。Objective To investigate the effect of resveratrol on apoptosis of ovarian cancer cells and its molecular mechanism,and to find a potential new target for the treatment of ovarian cancer.Methods Ovarian cancer SKOV-3 cells were divided into control group and resveratrol group.The survival rate of SKOV-3 cells treated with resveratrol was measured by MTT assay.24 h after resveratrol intervention in SKOV-3 cells,Western blot was used to detect the expression of Bcl-2,Bax,Caspase-3,HMGB1,TLR4 and NF-ĸB.Ovarian cancer SKOV-3 cells were transfected with si-NC,si-HMGB1,Rb1+pcDNA3.1 or Rb1+pcDNA3.1-HMGB1,and the sensitivity of cells to resveratrol was detected by MTT assay.The transfected cells were treated with resveratrol and apoptosis was detected by flow cytometry.Results Resveratrol could inhibit the growth of ovarian cancer SKOV-3 cells,and the higher the concentration of resveratrol,the more significant the inhibitory effect.The expression level of HMGB1 in control cells and resveratrol group was 1.24±0.15 and 0.86±0.11,respectively.25μM resveratrol inhibited HMGB1 protein level(P<0.01).The sensitivity to resveratrol was increased after HMGB1 was downregulated,and the apoptosis of SKOV-3 cells was promoted.HMGB1 overexpression increased the resistance to resveratrol and inhibited the apoptosis of SKOV-3 cells.TLR4 expression quantity control and resveratrol cells were 0.98±0.12 and 0.63±0.08,amount of NF-ĸB expression were 1.21±0.14 and 0.45±0.07,25μM resveratrol could cut TLR4 and NF-ĸB protein levels.Conclusions Resveratrol can promote apoptosis of ovarian cancer SKOV-3 cells.This mechanism may be related to the down-regulation of HMGB1/TLR4/NF-ĸB,which provides a basis for resveratrol treatment of ovarian cancer.

关 键 词：白藜芦醇 高迁移率组蛋白B1 SKOV-3细胞 凋亡 

分 类 号：R285[医药卫生—中药学]