Overexpression of SSTR2 inhibited the growth of SSTR2-positive tumors via multiple signaling pathways

Abstract

Background. Somatostatin receptors (SSTR1-5) are inhibitory G-protein coupled receptors that are ubiquitously expressed in both normal and cancer cells. Activation of SSTRs results in inhibition of hormone secretion and cell proliferation. Loss-of-expression of SSTR2 in tumor tissues has been suggested to correlate with tumor progression and to the relatively poorer outcomes of somatostatin analog treatment in some clinical trials. Therefore, gene transfer of SSTR2 has been studied extensively in those SSTR2-negative tumors. Material and methods. In this research, the anti-proliferation effects of overexpressed SSTR2 were studied in our experimental cancer xenografts with different profiles of endogenous SSTRs expression. An adenoviral vector was used to express full length human SSTR2 in capan-2 and A549 xenografts. The potential pathways involved in SSTR2 signaling were then studied using immunoassays. Results. Our results showed that overexpression of SSTR2 inhibited the growth of both SSTR2-positive and SSTR2-negative cancer xenografts. The SSTR2-mediated anti-proliferation involved both cytostatic (growth arrest) and cytotoxic (apoptotic) actions by affecting the cellular levels of signaling molecules in apoptotic pathway, MAPK pathway and angiogenesis. Conclusion. SSTR2 inhibits cancer growth via multiple pathways and is a potential candidate for gene therapy for both SSTR2-positive and SSTR2-negative tumors.