Autophagy contributes to the enrichment and survival of colorectal cancer stem cells under oxaliplatin treatment.
Currently, chemoresistance is an important cause of treatment failure in colorectal cancer. Cancer stem cells, which are a population of multi-potent cells with the capacity to self-renew and differentiate, have been found to participate in chemoresistance. In the present study, the chemotherapeutic drug oxaliplatin induced autophagy in colorectal cancer cell lines, which in turn protected cancer cells from apoptosis. Further results showed that oxaliplatin-induced autophagy enriched the population of colorectal CSCs and participated in maintaining the stemness of colorectal CSCs, thus making the cells more resistant to chemotherapy. Taken together, the results indicate that autophagy might enhance the chemoresistance of colorectal cancer cells by protecting the stemness and chemoresistance of colorectal CSCs. Our study demonstrates that autophagy plays a pro-survival role in colorectal CSCs subjected to oxaliplatin. Therefore, targeting autophagy may be considered as a potential therapeutic strategy to address chemoresistance in the treatment of colorectal cancer.
Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Hao-Zheng
HZ
Yang
Department of Biobank, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Yi
Y
Ma
Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Yan
Y
Zhou
Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Long-Mei
LM
Xu
Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Xiao-Jing
XJ
Chen
Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address: wbding@shsmu.edu.cn.
Wen-Bin
WB
Ding
Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address: coolice0917@163.com.
Han-Bing
HB
Zou
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin
Autophagy; Cancer stem cells; Chemoresistance; Colorectal cancer