Fusobacterium nucleatum prevents apoptosis in colorectal cancer cells via the ANO1 pathway

Pei Lu, Minyi Xu, Zhongbo Xiong, Fangfang Zhou, Lei Wang
 
Department of Clinical Laboratory, Shanghai No. 8 People’s Hospital, Shanghai, China
 
Correspondence: Pei Lu; Lei Wang
Department of Clinical Laboratory, Shanghai No. 8 People’s Hospital, No. 8, Caobao Road, Xuhui District, Shanghai 200235, China
Tel +86 21 3428 4588; +86 21 3428 4588
Email lu_pei@sohu.com;wolei6610@126.com
 
Objective: Chemotherapy failure derived from drug resistance is the most important reason causing the recurrence in colorectal cancer patients. Therefore, it is necessary to shed light on the mechanism of chemotherapy resistance in colorectal cancer patients.
Methods: We looked into the contribution of Fusobacterium nucleatum and ANO1 to chemoresistance in the human colorectal carcinoma cell lines. We silence and overexpress ANO1 in HCT116 and HT29 cells with lentivirus and siRNA knockdown technique in the absence or presence of F. nucleatum, oxaliplatin or 5-fluorouracil (5-FU). ANO1, p-pg, cleaved PARP, cleaved caspase-3, and EGFR expression was measured by Western blot. Cell apoptosis was measured by flow cytometry.
Results: We found that F. nucleatum promoted ANO1 expression on colon cancer cells. Moreover, ANO1 prevent colon cancer apoptosis from oxaliplatin and 5-FU. Additionally, knockdown ANO1 expression could block F. nucleatum protective effects and increase the apoptosis effects induced by oxaliplatin and 5-FU. Therefore, F. nucleatum might be biologically involved in the development of colon cancer chemoresistance via ANO1 pathway.
Conclusions: Taken together, our findings provide a valuable insight into clinical management and therapy, which may ameliorate colorectal cancer patient outcomes.
 
Keywords: colorectal cancer, F. nucleatum, chemoresistance, 5-fluorouracil, oxaliplatin, ANO1