中国病理生理杂志2023，Vol.39Issue(12)：2176-2184,9.DOI:10.3969/j.issn.1000-4718.2023.12.008
疏肝祛瘀解毒方介导p53通路诱导铁死亡抑制裸鼠肝癌生长的研究
Decoction for soothing liver and removing stasis and toxicity inhibits he-patocellular carcinoma proliferation in nude mice by inducing ferropto-sis via p53 pathway
摘要
Abstract
AIM:To investigate the inhibitory effect of the"decoction for soothing liver and removing stasis and toxicity(SGQYJDF)"on hepatocellular carcinoma(HCC)proliferation in nude mice by inducing ferroptosis via the tumor protein 53(p53)/solute carrier family 7 member 11(SLC7A11/xCT)/glutathione peroxidase 4(GPX4)pathway.METHODS:An ectopic subcutaneous tumor model was established by injecting SK-Hep-1 cells subcutaneously into the right axilla of nude mice.Upon formation of tumor,the mice were randomly divided into five groups(i.e.,control group,low-,medium-and high-dose SGQYJDF groups and medium-dose SGQYJDF plus Sorafenib group).Each group of mice was orally administered with the corresponding therapy for 14 consecutive days,during which the tumor size was observed regularly.At the end of treatment,the tumor growth inhibition rate was calculated based on tumor mass,and histopatho-logical changes were observed by HE staining.Then,the levels of malondialdehyde(MDA),glutathione(GSH)and fer-rous ions(Fe2+)were detected by colorimetric assays.The expression of the proliferation markers Ki-67 and GPX4 was de-tected by immunohistochemistry(IHC).The expression of p53 and xCT was detected by Immunofluorescence(IF).And the expression of p53,xCT and GPX4 was determined by Western blot.RESULTS:(1)SGQYJDF was found to dose-de-pendently decrease tumor volume(P＜0.01)and inhibit tumor mass growth(P＜0.01),and meanwhile,reduce the per-centage of Ki-67-positive cells(P＜0.01)and their proliferation ability in tumor tissues,as compared to the control group.(2)In terms of Ferroptosis-related indicators,SGQYJDF was found to dose-dependently increase the levels of Fe2+ and MDA but decrease the level of GSH in tumor tissues(P＜0.01),as compared to the control group.(3)In terms of protein expression,SGQYJDF was found to dose-dependently upregulate the expression of p53(P＜0.05)but inhibit the expres-sion of xCT(P＜0.05)and GPX4(P＜0.01).Notably,medium-dose SGQYJDF plus sorafenib showed a stronger effect than high-dose SGQYJDF.CONCLUSION:Our findings suggest that SGQYJDF can induce Ferroptosis to inhibit the proliferation of subcutaneously transplanted tumor tissues in nude mice by upregulating the expression of p53,and inhibit-ing the expression of xCT and GPX4.关键词
疏肝祛瘀解毒方/裸鼠移植瘤/肝细胞癌/铁死亡/肿瘤增殖Key words
decoction for soothing liver and removing stasis and toxicity/nude mouse xenograft tumor/hepa-tocellular carcinoma/ferroptosis/tumor proliferation分类
医药卫生引用本文复制引用
李菁,蔡晓钧,杨仁义,王智槟,朱姝静,瞿荧,钟崇..疏肝祛瘀解毒方介导p53通路诱导铁死亡抑制裸鼠肝癌生长的研究[J].中国病理生理杂志,2023,39(12):2176-2184,9.基金项目
国家自然科学基金面上项目(No.82274526) （No.82274526）
湖南省自然青年基金资助项目(No.2023JJ40503) （No.2023JJ40503）
湖南省中医肿瘤临床医学研究中心(No.2021SK4023) （No.2021SK4023）
湖南省临床医疗技术创新引导项目(No.2021SK51410) （No.2021SK51410）
湖南省卫生健康委科研重点项目(No.C202203108338) （No.C202203108338）
湖南省教育厅优秀青年项目(No.21B0365) （No.21B0365）
长沙市自然科学基金项目(No.kq2202453) （No.kq2202453）
