title: Growth Modulation of Diabetic Factors and Antidiabetic Drugs on Prostate Cancer Cell Lines.
abstract: Risk factors for prostate cancer (PCa) include age, hormones, race, family history and diet. Recently, epidemiologic evidence has indicated that history of diabetes mellitus (DM) is inversely associated with risk of PCa. However, epidemiological investigations have yielded inconsistent results. Hence, the exact mechanism of DM-induced reduction in the incidence of PCa has yet to be fully elucidated. The aim of this study was to investigate the effects of DM factors, including glucose, insulin and insulin-like growth factor-1 (IGF-1), on the proliferation of PCa cell lines in vitro. Cell proliferation and expression of hormone receptors was examined in MTT assay and Western blot analysis, respectively. The results showed that DM factors did not affect the viability of androgen receptor (AR)-expressing PCa cell lines. However, cell proliferation increased after treatment with DM factors in androgen-independent PCa cell lines. On PCa tissue arrays, intensities of total AR and nuclear IGF-1R were higher in malignant tissues than in normal prostate glands. In terms of hormonal receptors, androgen-dependent LNCaP cells treated with insulin and IGF-1 in a low-serum medium showed decreased expression of insulin receptor beta (IRβ) and elevated expression of IGF-1 receptor beta (IGF-1Rβ). Moreover, expression of AR was upregulated after insulin and IGF-1 treatment in LNCaP cells, but not in the other PCa cell lines. Most of the studied antidiabetic drugs promoted the viability of PCa cells. However, metformin decreased the viability of AR-expressing PCa cells. These results suggest that diabetic factors modify the expression of AR, IR and IGF-1R to increase cancer cell proliferation. Moreover, the growth suppressing effects of metformin on PCa may be via the regulation of the AR signaling pathway.
authors.affiliation: Department of Kidney, Tungs' Taichung Metroharbor Hospital, Taichung 43503, Taiwan, Republic of China.
authors.forename: Shiaw-Wen
authors.initials: SW
authors.lastname: Chien
authors.affiliation: Department of Physiology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Republic of China.
authors.forename: Dong-Yih
authors.initials: DY
authors.lastname: Kuo
authors.affiliation: Department of Physiology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Republic of China.
authors.forename: Jiuan-Miaw
authors.initials: JM
authors.lastname: Liao
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 40402.|Medical Center of Aging Research, China Medical University Hospital, Taichung 40447.|Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221.|Department of Biotechnology, College of Health Science, Asia University, Taichung 41354.|Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan, Republic of China.
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, Chung Shan Medical University, Taichung 40201.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, Republic of China.
authors.forename: Ching-Han
authors.initials: CH
authors.lastname: Yu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003920:Diabetes Mellitus / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000187:drug effects; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000187:drug effects; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D011944:Receptors, Androgen; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D005947:Glucose