Inhibition of metastatic progression of SSTR2 gene transfection mediated by adenovirus in human pancreatic carcinoma cells

Abstract

The inhibition of metastatic progression of Somatostatin receptor type 2 (SSTR2) gene transfection mediated by adenovirus in human pancreatic carcinoma cells and the mechanism involved in this effect were studied. The full-length human SSTR2 cDNA was introduced into the pancreatic cancer cell line BXPC-3 by adenovirus-mediated transfection. Stable expression of mRNAs and protein of SSTR2 was detected by RT-PCR and Western-blot. The Matrigel-coated Transwell was used to detect the migratory and invasive ability of SSTR2-expressing cells, Adv-GFP control cells and mock control cells. Furthermore, the expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) was detected by RT-PCR in these cells. The stable expression of SSTR2 was detected in BXPC-3 transfected by Adv-GFP-SSTR2. A dramatic decrease of BXPC-3 expressing sst2 cells migrating through a Matrigel-coated filter was observed, as compared with Adv-GFP control and mock control cells (P<0.01). Moreover, the expression of MMP-2 mRNA was significantly reduced in the SSTR2-expressing cells and conversely the expression of TIMP-2 mRNA was significantly increased in the SSTR2-expressing cells when compared with the Adv-GFP control and mock control (P<0.01). The expression of reintroduced human SSTR2 gene in BXPC-3 cells by Adv-GFP-SSTR2 had the anti-migratory and anti-invasive effects, and the mechanisms involved in this effect may be due to the down-regulated expression of MMP-2 and up-regulated expression of TIMP-2.

Keywords

pancreatic carcinoma / adenovirus vector / somatostatin receptor type 2 / metalloproteinase-2 / tissue inhibitor of metalloproteinase-2

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