Antagonists of growth hormone-releasing hormone (GH-RH) inhibit in vivo proliferation of experimental pancreatic cancers and decrease IGF-II levels in tumours

Abstract

Insulin-like growth factors (IGF-I and IGF-II) are implicated in the pathogenesis of pancreatic carcinoma. Antagonists of growth hormone-releasing hormone (GH-RH) suppress the GH-RH-GH-IGF-I axis and also act directly on tumours to reduce production of IGF-I or II.

The aim of this study was to investigate the effects of two potent GH-RH antagonists in two experimental models of pancreatic cancer.

Syrian golden hamsters with nitrosamine-induced pancreatic tumours were treated with 10 micrograms/day of GH-RH antagonist MZ-4-71 for 60 days.

The therapy reduced the number of tumorous animals, decreased the weight of tumorous pancreata by 55%, and lowered AgNOR numbers in tumour cells. In two other experiments, GH-RH antagonists MZ-4-71 and MZ-5-156 significantly inhibited growth of SW-1990 human pancreatic cancers xenografted into nude mice, as shown by a reduction in tumour volume and tumour weights, and a decrease in AgNORs in cancer cells. IGF-I levels in serum and in pancreatic cancer tissue remained unchanged after therapy, suggesting that an effect on IGF-I is not involved in tumour inhibition.

In contrast, IGF-II concentrations in tumours were significantly reduced by 50-60% after treatment with the GH-RH antagonists as compared with controls.

In vitro studies showed that the concentration of IGF-II in the culture medium was increased after seeding of SW-1990 cells, indicating that this pancreatic cancer cell line produced and released IGF-II. This finding was also supported by the expression of IGF-II mRNA in the SW-1990 cells.

Addition of 3 x 10(-6) M of GH-RH antagonist MZ-5-156 to the reduced-serum medium decreased cell proliferation, IGF-II mRNA expression in the cells and IGF-II concentration in the medium.

Our findings indicate that inhibitory effects of GH-RH antagonists on the growth of experimental pancreatic cancers, may result from a decrease in the production and concentration of IGF-II in the tumours.

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See also:

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- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;

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- Excellent result in a Mesothelioma case treated exclusively with Di Bella Method for over 4 years and still treatment with positive results;

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- Oesophageal squamocellular carcinoma: a complete and objective response;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature.