[Mechanisms of inhibition of growth of human pancreatic carcinoma implanted in nude mice by somatostatin receptor subtype 2]

Abstract

Objective: To investigate the antitumor effect of somatostatin receptor subtype 2 (SSTR2) gene transfection into pancreatic cancer cell line PC-3, and the mechanisms involved in this effect.

Methods: The full-length human SSTR2 cDNA was introduced into the pancreatic cancer cell line PC-3 by lipofect amine-mediated transfection. Positive clones were screened by G418 and stable expression of SSTR2 was detected by immunocytochemistry SABC method and RT-PCR. Fifteen athymic mice were randomly divided into 3 groups of 5 mice to be xenografted with SSTR2-expressing cells (experimental group), empty vector control group, and control group cells respectively. The weight of mice and the size of tumor were measured every week. Eight weeks later the mice were killed and the tumors were taken out. TUNEL assay was used to determine the apoptotic index (AI) in these tumors. Immunohistochemistry SP method was used to determine the expressions of apoptosis regulating genes, Bcl-2 and Bax, and intratumoral. microvessel density (MVD). Moreover, the tumor volume and weight were compared among these three groups.

Results: The AI was significantly higher in the experimental group (3.39% +/- 0.84%) compared with the empty vector control group (0.69% +/- 0.08%) and control group (0.68% +/- 0.09%) (both P < 0.05). The significant decrease in Bcl-2, and increase in Bax protein expressions were detected in the experimental group compared with the empty vector control group and control group (both P < 0.05). MVD was significantly lower in the experimental group (6.3 +/- 1.7) than those in the empty vector control group (12.6 +/- 1.7) and control group (13.5 +/- 1.9) (P < 0.05). Moreover, the tumor volume and weight were significantly lower in the experimental group as compared with the empty vector control group and control group (P < 0.05). However, no significant differences in all the indicators were observed between the empty vector control group and the control group (both P > 0.05).

Conclusions: Re-expression of SSTR2 gene, the expression of which is frequently lost in human pancreatic adenocarcinoma, can induce apoptosis which may be mediated via down-regulation of Bcl-2 and up-regulation of Bax, and inhibit tumor angiogenesis in pancreatic carcinoma, resulting in inhibition of tumor growth.