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Growth Hormone differentially modulates chemoresistance in human endometrial adenocarcinoma cell lines

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Abstract

Growth Hormone may influence neoplastic development of endometrial epithelium towards endometrial adenocarcinoma, which is one of the most occurring tumors in acromegalic patients. Since chemoresistance often develops in advanced endometrial adenocarcinoma, we investigated whether Growth Hormone might influence the development of chemoresistance to drugs routinely employed in endometrial adenocarcinoma treatment, such as Doxorubicin, Cisplatin, and Paclitaxel. Growth Hormone and Growth Hormone receptor expression was assessed by immunofluorescence in two endometrial adenocarcinoma cell lines, AN3 CA and HEC-1-A cells. Growth Hormone effects were assessed investigating cell viability, caspase3/7 activation, ERK1/2, and protein kinase C delta protein expression. AN3 CA and HEC-1-A cells display Growth Hormone and Growth Hormone receptor. Growth Hormone does not influence cell viability in both cells lines, but significantly reduces caspase 3/7 activation in AN3 CA cells, an effect blocked by a Growth Hormone receptor antagonist. Growth Hormone rescues AN3 CA cells from the inhibitory effects of Doxorubicin and Cisplatin on cell viability, while it has no effect on Paclitaxel. Growth Hormone does not influence the pro-apoptotic effects of Doxorubicin, but is capable of rescuing AN3 CA cells from the pro-apoptotic effects of Cisplatin. On the other hand, Growth Hormone did not influence the effects of Doxorubicin and Paclitaxel on HEC-1A cell viability. The protective action of Growth Hormone towards the effects of Doxorubicin may be mediated by ERK1/2 activation, while the pro-apoptotic effects of Cisplatin may be mediated by protein kinase C delta inhibition. All together our results indicate that Growth Hormone may differentially contribute to endometrial adenocarcinoma chemoresistance. This may provide new insights on novel therapies against endometrial adenocarcinoma chemoresistant aggressive tumors.

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Acknowledgments

This work was supported by grants from the Italian Ministry of Education, Research and University (FIRB RBAP11884M, RBAP1153LS), and Associazione Italiana per la Ricerca sul Cancro (AIRC) in collaboration with Laboratorio in rete del Tecnopolo “Tecnologie delle terapie avanzate” (LTTA) of the University of Ferrara. The funding sources had no involvement in study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication. We thank Pfizer Italy for providing Pegvisomant pure substance.

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  1. Section of Endocrinology and Internal Medicine, Dept. of Medical Sciences, University of Ferrara, Ferrara, Italy

    Erica Gentilin, Mariella Minoia, Marta Bondanelli, Federico Tagliati, Ettore C. degli Uberti & Maria Chiara Zatelli

  2. Laboratorio in rete del Tecnopolo “Tecnologie delle terapie avanzate” (LTTA) of the University of Ferrara, Ferrara, Italy

    Ettore C. degli Uberti & Maria Chiara Zatelli

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  1. Erica Gentilin
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Gentilin, E., Minoia, M., Bondanelli, M. et al. Growth Hormone differentially modulates chemoresistance in human endometrial adenocarcinoma cell lines. Endocrine 56, 621–632 (2017). https://doi.org/10.1007/s12020-016-1085-4

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