title: Glargine promotes proliferation of breast adenocarcinoma cell line MCF-7 via AKT activation.
abstract: Glargine is widely used as a long-acting insulin analogue in the treatment of diabetes mellitus. However, this insulin analogue has been recently suspected to be associated with an increased risk of cancer. The aim of this study was to investigate the influence of glargine on proliferation of breast adenocarcinoma cell line (MCF-7) and its possible mechanism. Effects of glargine and regular human insulin on the cell proliferation were tested in ER-positive MCF-7 cells by MTT assay. Apoptosis in MCF-7 cells was measured by flow cytometry. The protein levels of p-AKT, Bcl-2, and Bax were also determined by Western blotting and immunohistochemistry, respectively. The result showed that glargine (100, 200 nmol/l) stimulated proliferation of ER-positive MCF-7 cells compared with regular human insulin. At the same time, glargine decreased the percentage of early apoptosis in MCF-7 cells. Otherwise, glargine (100 nmol/l) stimulated the p-AKT in a time-dependent manner in MCF-7 cells. Furthermore, we found that glargine downregulated the level of Bax protein and upregulated that of Bcl-2 (p <0.05). These data show that glargine promote the proliferation of breast adenocarcinoma cells in vitro, probably by preventing apoptosis.
authors.affiliation: Department of Cadre Medicine, The Hospital of Guangxi Zhuang Autonomous Region, Guangxi, P. R. China.
authors.forename: J-A
authors.initials: JA
authors.lastname: Teng
authors.forename: R-L
authors.initials: RL
authors.lastname: Hou
authors.forename: D-L
authors.initials: DL
authors.lastname: Li
authors.forename: R-P
authors.initials: RP
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Qin
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D049528:Insulin, Long-Acting; D051028:bcl-2-Associated X Protein; D000069036:Insulin Glargine; D051057:Proto-Oncogene Proteins c-akt