文献类型：期刊文献

英文题名：Realgar-induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis

作者：Liu, Xiaofeng[1];Hai, Yang[3,4,5];Dong, Jinqu[1];Xu, Lan[1];Hou, Wenqian[1];Su, Jing[1];Ren, Weiyu[1];Liu, Dongling[1,2,4,6]

第一作者：刘雪枫

通信作者：Liu, DL[1]

机构：[1]Gansu Univ Chinese Med, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Prov Key Lab Pharmacol & Toxicol TCM, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Sci Res & Expt Ctr, Lanzhou 730000, Gansu, Peoples R China;[4]Northwest Collaborat Innovat Ctr Tradit Chinese Me, Lanzhou 730000, Gansu, Peoples R China;[5]Res Ctr Tradit Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[6]Gansu Univ Chinese Med, Sch Pharm, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Pharm, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2022

卷号：61

期号：6

外文期刊名：INTERNATIONAL JOURNAL OF ONCOLOGY

收录：;Scopus(收录号：2-s2.0-85141205102);WOS:【SCI-EXPANDED(收录号:WOS:000882107600001)】；

语种：英文

外文关键词：realgar; KRAS-mutant; lung cancer; apoptosis; ferroptosis

摘要：KRAS is a biomarker for non-small cell lung cancer-targeted therapy, but there is currently no effective KRAS-targeting medication. Realgar is an impelling anti-cancer drug, however its significance in KRAS mutant lung cancer is uncertain. According to our findings, the IC50 of H23 (KRAS mutant) cells is 2.99 times lower than that of H1650 (non-KRAS mutant) cells. Flow cytometry and the Hoechst 33258 staining assay revealed that H1650 cells treated with 4 mu g/ml realgar had an apoptotic rate of 8.2%, while H23 cells had a rate of 21.46%. Accordingly, realgar was more sensitive to KRAS mutant cells. Transcriptome sequencing test indicated that there were 481 different expression genes in H23 cells treated with realgar. In H23 cells treated with realgar, mitochondria shrank, inner membrane folding was disturbed, and mitochondrial membrane potential crushed. Realgar boosted intracellular Fe2+, reactive oxygen species, malondialdehyde and glutathione levels, which were all reversed by ferroptosis inhibitor Fer-1. Realgar decreased phosphorylated p-Raf, p-ERK1/2 and increased p-p38 and p-JNK, whereas only p-Raf was abolished by Fer-1. Raf inhibitor Sorafenib accelerated the realgar-induced ferroptosis. On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in anti-KRAS mutant lung cancer.