Insulin analogs detemir, glargine and lispro enhance proliferation of human thyroid and gastric normal or cancer cell lines

Previous studies indicate that insulin associated signals can activate the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways, resulting in metabolic and mitogenic effects. The purpose of our study was to investigate the influence of the insulin analogs Detemir, Aspart, Glargine and Lispro on the human cancer cell cultures. We incubated thyroid cell line HTori3; thyroid cancer cell lines K1, 8305c, FTC133, normal gastric cell line GES-1, and gastric cancer cell lines MGC803 SGC7901 BGC823 with insulin, insulin-like growth factor-1 (IGF-1) or insulin analogs Detemir, Aspart, Glargine and Lispro, and assessed proliferation by MTT assay, apoptosis by flow cytometry and cell invasion with transwell cultures. In addition, phosphorylation of signaling molecules was detected by immunoblot. Detemir, Glargine and Lispro induced proliferation of K1 and HTori3, but had no effect on cell invasion of 8305c or SGC7901 cells. These insulin analogs varied in their capacity to induce proliferation in these cell lines, but all compounds increased the rate of apoptosis in all cell lines. ERK phosphoryla­tion was not observed in response to insulin, IFG-1 or Glargine in GES-1, MGC803, BGC823 or HTori3 cells, however was observed in response to insulin, IFG-1 or Glargine in K1 and FTC133. Enhanced Akt phosphorylaition was not observed in any condition. Insulin analogs Detemir, Glargine and Lispro, but not Aspart, induce proliferation of nor­mal and cancerous thyroid and gastric cell lines. The enhancement of proliferation mediated by insulin analogs in thyroid cancer cell lines may be mediated by ERK phosphorylation.