Autocrine human growth hormone reduces mammary and endometrial carcinoma cell sensitivity to mitomycin C

Abstract

Drug resistance is a major cause of chemotherapy failure in breast cancer patients with metastatic disease.

We previously demonstrated that autocrine human growth hormone (hGH) plays a key role in oncogenic transformation and progression of mammary carcinoma.

The present study investigated the role of autocrine hGH in the development of resistance to mitomycin C (MMC), an alkylating agent utilised in the treatment of advanced metastatic breast cancer.

Stable forced expression of the hGH gene was established in the mammary carcinoma cell lines MDA-MB-231, MCF-7 and T47D. Autocrine hGH reduced the sensitivity of mammary carcinoma cells to MMC in cell viability assays and reduced MMC-induced apoptotic cell death when compared to a control cell line.

In addition, autocrine hGH enhanced MDA-MB-231 clonogenic survival, anchorage independent cell growth, growth in 3D Matrigel and protected MDA-MB-231 cells from induction of DNA double-strand breaks following MMC treatment.

Functional antagonism of hGH in the endometrial carcinoma cell line RL95-2, which endogenously expresses hGH, significantly increased the sensitivity of these cells to MMC-induced DNA damage and cell death.

Thus, autocrine hGH promotes mammary and endometrial carcinoma cell resistance to MMC.

These studies indicate a potential role for antagonism of autocrine hGH in chemoresistant breast cancer.

 

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See also:

- Official Web Site: The Di Bella Method;

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

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

- 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.