Acta Pharmacologica Sinica (2009) 30: 1053-1059; doi: 10.1038/aps.2009.59

Aim: Somatostatin receptor subtype 2 (SSTR2) is the principal mediator of somatostatin’s (SST) antiproliferative effects on normal and cancer cells.  Therefore, we investigated whether the enhanced expression of SSTR2 could inhibit the proliferation of tumor cells, and, if so, the mechanisms that might be involved.   

Methods: SSTR2 expression levels were determined by qRT-PCR in several tumor cell lines.  Then, a plasmid pIRES2-EGFP-SSTR2 (pSIG) was constructed and stably transfected into MCF-7 cells (MCF-7/pSIG).  After SSTR2 overexpression was identified by qRT-PCR, immunofluorescence staining and a receptor binding assay, the MCF-7/pSIG cells were analyzed by PI staining for apoptosis and cell cycle arrest was tested by flow cytometry for epidermal growth factor receptor (EGFR) expression.  The EGF-stimulated proliferation of MCF-7 cells was assayed by MTT.   

Results: The human breast cancer cell line MCF-7 expresses a lower level of SSTR2, thereby partly accounting for the decreased response to SST.  The overexpression of SSTR 2 in MCF-7 cells resulted in apoptosis, cytostasis and G₁/S cell cycle arrest.  Furthermore, the expression of EGFR, together with EGF-stimulated proliferation, was markedly decreased in the MCF-7/pSIG cells.

Conclusion: Enhanced SSTR2 expression played an antiproliferative role in MCF-7 cells through inducing apoptosis and G₁/S cell cycle arrest, and also by decreasing EGFR expression, thereby counteracting the growth-stimulating effect of EGF.  Our data seem to indicate that developing a new therapeutic agent capable of upregulating SSTR expression could potentially be a way to block tumor progression.

Keywords: somatostatin; somatostatin receptor; epidermal growth factor receptor; breast cancer