Decoction for soothing liver and removing stasis and toxicity inhibits he-patocellular carcinoma proliferation in nude mice by inducing ferropto-sis via p53 pathway
10.3969/j.issn.1000-4718.2023.12.008
- VernacularTitle: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
- Author:
Jing LI
1
;
Xiaojun CAI
;
Renyi YANG
;
Zhibin WANG
;
Shujing ZHU
;
Ying QU
;
Chong ZHONG
Author Information
1. 湖南中医药大学第一附属医院,湖南 长沙 410007
- Keywords:
decoction for soothing liver and removing stasis and toxicity;
nude mouse xenograft tumor;
hepa-tocellular carcinoma;
ferroptosis;
tumor proliferation
- From:
Chinese Journal of Pathophysiology
2023;39(12):2176-2184
- CountryChina
- Language:Chinese
-
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.
