评估胰岛素类似物在子宫内膜癌细胞系中的生物作用

EVALUATION OF THE BIOLOGICAL ACTIONS OF INSULIN ANALOGUES IN ENDOMETRIAL CANCER CELL LINES

Background: Modifications introduced into native insulin molecules may enhance their affinity for the IGF-I receptor (IGF-IR). The IGF-IR, which displays a close similarity to the insulin receptor (IR), has been correlated with a number of neoplastic processes. Endometrial cancer exhibits a significant association with obesity and diabetes. We hypothesized that insulin analogues may elicit atypical proliferative and signaling activities in endometrial cancer cells.
Methods: The ECC-1 and USPC-1 endometrial cancer cell lines were used in this study. Proliferative and anti-apoptotic effects of insulin analogues were determined by MTT assays and PARP measurements, respectively. The signaling pathways elicited by the analogues were assessed by Western blot.
Results: MTT assays revealed that insulin glargine increased proliferation rates in both cell lines. The proliferative response in ECC-1 cells displayed a dose-dependent curve whereas, in contrast, cells exposed to IGF-I and regular insulin reached plateau values. In addition, apoptosis measurements demonstrated that insulin glargine prevented PARP cleavage in USPC-1 cells. Furthermore, both insulin glargine and detemir were able to induce AKT and ERK phosphorylation in both endometrial cancer cell lines.
Conclusions: Our data indicate that long-acting insulin analogue glargine, but not detemir, exhibits IGF-I-like proliferative and anti-apoptotic effects in both endometrial cancer cell lines. Short-acting insulin analogues lispro and aspart exhibit enhanced proliferative activities only in ECC cells. Finally, insulin glargine and detemir elicit atypical signaling activities in both cell lines. The clinical implications of the biological actions of insulin analogues in endometrial cancer must be critically evaluated.

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