Endocrine Abstracts

Background: Surgery is the main therapeutic option for advanced endometrial cancer; however, when disease relapses, chemotherapy is the only option. Chemoresistance is a very common phenomenon in these tumors. We previously demonstrated that GH protects breast cancer cells towards the cytotoxic effects of doxorubicin, inducing chemoresistance. Recent evidences show that endometrial cancer cells secrete GH, stimulating their own growth in an autocrine fashion.

Aim: To evaluate whether GH may impact on sensitivity of HEC1A and AN3CA endometrial cancer cell lines to Doxorubicin (D) and Cisplatin (C) and to investigate the possible implicated mechanisms.

Methods: Two endometrial cancer cell lines were used to carry out this study: the HEC-1A cell line, expressing the estrogen receptor (ER), and the AN3CA cell line, which does not express ER. To evaluate cell viability we performed ATPlite assay and to assess apoptosis activation we performed a Caspase 3–7 activity assay. To evaluate protein expression, we performed western blot analysis.

Results: GH protected endometrial cancer cells from D- and C-induced apoptosis. In addition, GH reduced D- and C-induced ERK 1/2 phosphorylation and PKCδ expression, both involved in chemotherapic-dependent apoptosis. These effects were reduced by Pegvisomant, a GH receptor antagonist.

Conclusion: GH promotes resistance to apoptosis induced by chemotherapeutic drugs by modulating the apoptotic pathway, inhibiting ERK1/2 phosphorylation and PKCδ expression. These findings support the hypothesis that blocking GH receptor may be viewed as a potential new therapeutic approach to overcome chemoresistance in endometrial cancer.