Inhibition of growth and metastases of MDA-MB-435 human estrogen-independent breast cancers by an antagonist of growth hormone-releasing hormone

Abstract

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit the growth of various cancers by mechanism(s) that include the suppression of the insulin-like growth factors (IGF)-I and/or -II.

In this study, nude mice bearing orthotopic implants of MDA-MB-435 human estrogen-independent breast carcinoma received 39 days of therapy with GH-RH antagonist JV-1-36 (20 microg/day).

The treatment significantly inhibited tumor growth by 71.1% (p<0.01) and nullified the metastatic potential of MDA-MB-435 cells. Four of eight control mice (50%) developed metastases in the lymph nodes and one (12.5%) in the lung, but none of the animals receiving JV-1-36 showed metastatic spread.

GH-RH antagonist JV-1-36 inhibited the growth of MDA-MB-435 cells in vitro, while IGF-I stimulated it. However, mRNA for IGF-I or -II was not detected in MDA-MB-435 cells, indicating that the suppression of autocrine IGFs may not be involved in the antiproliferative mechanism.

Using ligand competition assays with (125)I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-polymerase chain reaction revealed the expression of mRNA for GH-RH receptor splice variant-1 in MDA-MB-435 tumors.

Our results suggest that the antitumorigenic action of GH-RH antagonists on MDA-MB-435 breast cancer could be direct and mediated by tumoral GH-RH receptors.

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See also:

- Official Web Site: The Di Bella Method;

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- The Di Bella Method (A Variable Part - Selenium methonine, 40 μg capsules, twice a day);

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

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