Growth Hormone Excess Promotes Breast Cancer Chemoresistance

Abstract

Context: GH and IGF-I are known to promote breast carcinogenesis. Even if breast cancer (BC) incidence is not increased in female acromegalic patients, mortality is greater as compared with general population.

Objective: The objective of the study was to evaluate whether GH/IGF-I excess might influence BC response to chemotherapy.

Design: We evaluated GH and IGF-I effects on cell proliferation of a BC cell line, MCF7 cells, in the presence of doxorubicin (Doxo), frequently used in BC chemotherapy, and the possible mechanisms involved.

Results: GH and IGF-I induce MCF7 cell growth in serum-free conditions and protect the cells from the cytotoxic effects of Doxo. GH effects are direct and not mediated by IGF-I because they are apparent also in the presence of an IGF-I receptor blocking antibody and disappear in the presence of the GH antagonist pegvisomant. The expression of the MDR1 gene, involved in resistance to chemotherapeutic drugs, was not induced by GH. In addition, c-fos transduction was reduced by Doxo, which prevented GH stimulatory effects. Pegvisomant inhibited basal and GH-induced c-fos promoter transcriptional activity. Autocrine GH action is ruled out by the lack of endogenous GH expression in this MCF7 cell strain.

Conclusions: These data indicate that GH can directly induce resistance to chemotherapeutic drugs with a mechanism that might involve GH-induced early gene transcription and support the hypothesis that GH excess can hamper BC treatment, possibly resulting in an increased mortality.

 

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer.