title: Effects of metformin on CD133+ colorectal cancer cells in diabetic patients.
abstract: In diabetic patients complicated with colorectal cancer (CRC), metformin treatment was reported to have diverse correlation with CRC-specific mortality. In laboratory studies, metformin was reported to affect the survival of cancer stem cells (CSCs) in breast and pancreatic cancers and glioblastoma. Although cscs play a critical role in the resistance to 5-fluorouracil (5-FU) chemotherapy in CRC patients, the effect of metformin on cscs in CRC patients and the synergistic effect of metformin in combination with 5-FU on cscs are not reported. In the present study pathological examinations were performed in 86 CRC patients complicated with type 2 DM who had been divided into a metformin group and a non-metformin group. Comparisons regarding pathological type, incidence of metastasis, expression of CD133 and β-catenin were conducted between the two groups. We explored the synergistic effects of metformin in combination with 5-FU on the proliferation, cell cycle, apoptosis and the proportion of CD133+ cscs of SW620 human colorectal cancer cell lines. The results show that metformin treatment had reverse correlations with the proportion of patients with poorly differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with type 2 DM. Metformin enhanced the antiproliferative effects of 5-FU on CD133+ cscs in SW620 cells. These findings provide an important complement to previous study. Inhibition of the proliferation of CD133+ cscs may be a potential mechanism responsible for the association of metformin use with improved CRC outcomes in CRC patients with type 2 diabetes.
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Meiping
authors.initials: M
authors.lastname: Guan
authors.forename: Zongji
authors.initials: Z
authors.lastname: Zheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D006023:Glycoproteins; D007004:Hypoglycemic Agents; C000606023:PROM1 protein, human; D010455:Peptides; D051176:beta Catenin; D008687:Metformin; D005472:Fluorouracil