title: Diet-induced hyperinsulinemia accelerates growth of androgen-independent PC-3 cells in vitro.
abstract: We investigated the effect of insulin and diet-induced hyperinsulinemia on the growth of the PC-3 cells in vitro and discerned the growth promoting effect of insulin in the androgen-independent cells. Sprague-Dawley rats were kept on a high-fat diet for 4 wk for the induction of insulin resistance and hyperinsulinemia. Insulin alone or serum of the rats kept on either normal-pellet diet or high-fat diet was used to stimulate the serum-starved PC-3 cells growth in culture. S961, a high-affinity insulin-receptor antagonist, was used to confirm the insulin-mediated effects. Significant impairment in the glucose disposal rate and increase in the serum glucose and insulin levels was observed in the high-fat-diet-fed rats. The media supplemented with the serum of the high-fat-diet-fed rats accelerated the growth of the PC-3 cells in comparison to that of normal-pellet-diet-fed rats. Insulin treatment led to accelerated growth of the serum-starved PC-3 cells in a dose-dependent manner and inhibited by the S961 pretreatment. Insulin and serum of the diet-induced hyperinsulinemic rats promote the growth of androgen-independent prostate cancer PC-3 cells. Further, our results provide support for the concept that diet-associated elevation in insulin level may augment the growth of prostate cancer cells.
authors.affiliation: Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, Punjab, India.
authors.forename: Ajit
authors.initials: A
authors.lastname: Vikram
authors.forename: Gopabandhu
authors.initials: G
authors.lastname: Jena
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D010455:Peptides / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors
chemical_list: D000728:Androgens; D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; C532752:S961 peptide; D011972:Receptor, Insulin