Aldehyde dehydrogenase 2 family member repression promotes colorectal cancer progression by JNK/p38 MAPK pathways-mediated apoptosis and DNA damage  

作　　者：Miao Yu Qian Chen Yi-Ping Lu 

机构地区：[1]Department of Surgical Oncology,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China [2]Clinical School of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第7期3230-3240,共11页世界胃肠肿瘤学杂志(英文)

基　　金：Supported by Beijing Municipal Hospital Research and Cultivation Program Project,No.PZ2022008.

摘　　要：BACKGROUND Aldehyde(ALDH2)dysfunction has been verified to contribute to human cancers.AIM To investigate the molecular mechanism and biological function of ALDH2 in colorectal cancer(CRC)progression.METHODS Human CRC cells with high expression of ALDH2 were screened.After shRNA ALDH2(sh-ALDH2)transfection,phenotypes[proliferation,apoptosis,acetaldehyde(ACE)accumulation,DNA damage]of CRC cells were verified using cell counting kit-8,flow cytometry,ACE assay,and comet assays.Western blotting was used for evaluation of the apoptosis proteins(Bax and Bcl-2)and JNK/p38 MAPK pathway-associated proteins.We subjected CVT-10216(a selective ALDH2 inhibitor)to nude mice for establishment of SK-CO-1 mouse xenograft model and observed the occurrence of CRC.RESULTS The inhibition of ALDH2 could promote the malignant structures of CRC cells,including apoptosis,ACE level,and DNA damage,and cell proliferation was decreased in the sh-ALDH2 group,whereas ALDH2 agonist Alda-1 reversed features.ALDH2 repression can cause ACE accumulation,whereas ACE enhanced CRC cell features related to increased DNA damage.Additionally,ALDH2 repression led to JNK/P38 MAPK activation,and apoptosis,ACE accumulation,and DNA damage were inhibited after p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125 addition.ACE accumulation and raised DNA damage were recognized in CVT-10216 treated-mouse tumor tissues in vivo.CONCLUSION The repression of ALDH2 led to ACE accumulation,inducing cell apoptosis and DNA damage by the JNK/p38 MAPK signaling pathway activation in CRC.

关 键 词：Aldehyde dehydrogenase 2 family member Colorectal cancer ACETALDEHYDE Apoptosis DNA damage JNK/p38 MAPK 

分 类 号：R73[医药卫生—肿瘤]