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.

ACKNOWLEDGMENTS

We wish to acknowledge the financial assistance received for this experimentation from the National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, India. We further place on record our heartfelt gratitude to Dr. Lauge Schaffer, Novo Nordisk, Denmark for kindly providing S961.