Introduction: It is known that growth hormone (GH) may influence neoplastic development of endometrial epithelium. GH is produced by normal and neoplastic endometrial cells and elevated levels have been observed in endometrial epithelium of patients with endometriosis and endometrial adenocarcinoma (EA). Moreover, endometrium cancer is one of the most occurring tumors in acromegalic patients. Furthermore, autocrine GH increases the oncogenicity of EA cells and is considered fundamental in neoplastic progression. Since chemoresistance often develops in advanced EA, we aimed at investigating whether GH might influence the development of chemoresistance to drugs routinely employed in EA treatment.
Description of methods: To this aim we employed two EA cell lines: HEC-1-A and AN3 CA cells. Cell viability and caspase activation were assessed by CellTiter-Glo Luminescent Cell Viability Assay (Promega) and Caspase-Glo 3/7 Assay (Promega), respectively. The expression of protein chinase C delta (PRKCD) was investigated by Western-blotting.
Results: We demonstrated that GH increases the viability of EA cell lines, while doxorubicin, cisplatin and paclitaxel significantly reduce this parameter. GH was capable to blunt the effects of doxorubicin and cisplatin, but did not influence paclitaxel effects on cell viability. GH also protects EA cells from caspase activation induced by doxorubicin and cisplatin. In addition, doxorubicin and cisplatin induce PRKCD expression, an effect counteracted by GH.
Conclusion: All together our results suggest that GH may contribute to EA chemoresistance by interfering with apoptotic mechanisms. This may provide new insights on novel therapies against EA chemoresistant aggressive tumors.