Somatostatin inhibits colon cancer cell growth through cyclooxygenase-2 downregulation

Abstract

BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2) is expressed in colonic neoplasms, where it supports cell proliferation via prostaglandin E(2) (PGE(2)) production. This study investigated the effects of somatostatin-14 on COX-2 expression, PGE(2) production and proliferation in colon cancer cells.

EXPERIMENTAL APPROACH: Human colon adenocarcinoma cell lines Caco-2, HT-29 and HCT116 were used. The following techniques were employed: colourimetric assay for cell growth; 5-bromo-2'-deoxyuridine assay for DNA synthesis; enzyme immunoassay for PGE(2); COX-2 mRNA silencing; RT-PCR or Western blot for somatostatin receptor subtypes, cyclooxygenase isoforms, phosphorylated-ERK-1/ERK-2 and phosphorylated-Akt.

KEY RESULTS: HT-29 and Caco-2 cells expressed COX-2 and somatostatin receptors (sst(3/4/5) and sst(3/5), respectively). HCT116 cells did express somatostatin receptors (sst(2/3/5)), but not COX-2. Somatostatin-14 inhibited basal COX-2 expression, PGE(2) production, DNA synthesis and growth in Caco-2 cells and these effects were prevented by BN81658 (sst(3) receptor antagonist). Basal proliferation of HT-29, HCT116 and COX-2-silenced Caco-2 cells was not affected by somatostatin-14. Stimulation of HT-29 cells with gastrin-17 elicited increments of ERK-1/ERK-2 and Akt phosphorylation, COX-2 expression, PGE(2) production, DNA synthesis and cell growth, which were all counteracted by somatostatin-14. Somatostatin-14-induced inhibition of COX-2 expression, PGE(2) production and DNA synthesis were blocked by BIM23056 (sst(5) receptor antagonist).

CONCLUSIONS AND IMPLICATIONS: Somatostatin decreases COX-2 expression and function in colon cancer cells via activation of sst(3) or sst(5) receptors, and these effects contribute to the inhibitory action of somatostatin on cell proliferation. These findings can be relevant to the development of therapeutic strategies based on the modulation of the COX-2 pathway.

 

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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);

- 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;

- 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.