Enhancing the radiosensitivity of colorectal cancer cells by reducing spermine synthase through promoting autophagy and DNA damage  

作　　者：Yu-Bin Guo Yue-Ming Wu Zhi-Zhao Lin 

机构地区：[1]Guangdong Provincial Key Laboratory of Gastroenterology,Department of Gastroenterology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第12期4716-4727,共12页世界胃肠肿瘤学杂志（英文）

基　　金：Supported by National Natural Science Foundation of China,No.82102996;Guangdong Provincial Natural Science Foundation,No.2022A1515010517;Guangzhou Science and Technology Plan Project,No.202201011016;President Foundation of Nanfang Hospital,Southern Medical University,No.2020C038.

摘　　要：BACKGROUND Colorectal cancer(CRC),the third most common cancer worldwide,has increasingly detrimental effects on human health.Radiotherapy resistance diminishes treatment efficacy.Studies suggest that spermine synthase(SMS)may serve as a potential target to enhance the radiosensitivity.AIM To investigate the association between SMS and radiosensitivity in CRC cells,along with a detailed elucidation of the underlying mechanisms.METHODS Western blot was adopted to assess SMS expression in normal colonic epithelial cells and CRC cell lines.HCT116 cells were transfected with control/SMS-specific shRNA or control/pcDNA3.1-SMS plasmids.Assessments included cell viability,colony formation,and apoptosis via MTT assays,colony formation assays,and flow cytometry.Radiosensitivity was studied in SMS-specific shRNA-transfected HCT116 cells post-4 Gy radiation,evaluating cell viability,colony formation,apoptosis,DNA damage(comet assays),autophagy(immunofluorescence),and mammalian target of rapamycin(mTOR)pathway protein expression(western blot).RESULTS Significant up-regulation of SMS expression levels was observed in the CRC cell lines.Upon down-regulation of SMS expression,cellular viability and colonyforming ability were markedly suppressed,concomitant with a notable increase in apoptotic indices.Furthermore,attenuation of SMS expression significantly augmented the sensitivity of HCT116 cells to radiation therapy,evidenced by a pronounced elevation in levels of cellular DNA damage and autophagy.Impor tantly,down-regulation of SMS corresponded with a marked reduction in the expression levels of proteins associated with the mTOR signaling pathway.CONCLUSION Knocking down SMS attenuates the mTOR signaling pathway,thereby promoting cellular autophagy and DNA damage to enhance the radiosensitivity of CRC cells.

关 键 词：Spermine synthase Colorectal cancer RADIOSENSITIVITY AUTOPHAGY DNA damage 

分 类 号：R735[医药卫生—肿瘤]