Gene transfer of somatostatin receptor type 2 by intratumoral injection inhibits established pancreatic carcinoma xenografts

World J Gastroenterol. 2005 Jan 28;11(4):516-20. doi: 10.3748/wjg.v11.i4.516.

Abstract

Aim: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers.

Methods: Human pancreatic cancer cell line Panc-1 was inoculated subcutaneously into the back of nude mice. When tumor nodules were grown as large as about 5 mmX5 mm days after inoculation, the mice were randomly divided into 3 groups (6 mice in each group). Group I served as untreated control group. Group II received an intratumoral injection of a combination of human cytomegalovirus promoter-6C (pCMV-6C) and lipofectamine 2000. Group III received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000. The rate of tumor growth was compared among these three groups. The expression of SSTR2 in these tumors was detected by immunohistochemistry and Western-blot. Apoptosis index (AI) in these tumors was examined by using TUNEL in situ.

Results: Intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000 resulted in the expression of SSTR2 protein. The tumor size and weight in group III (0.318+/-0.098 cm3, and 0.523+/-0.090 g, respectively) were significantly lower than those in group I (2.058+/-0.176 cm3, and 1.412+/-0.146 g, respectively) and group II (2.025+/-0.163 cm3, and 1.365+/-0.116 g, respectively) (P<0.05) The AI in group III (1.47+/-0.13%) was significantly higher than that in group I (0.56+/-0.09%) and group II (0.57+/-0.11%) (P<0.05). But there were no significant differences between groups I and II.

Conclusion: Our data demonstrate that re-expression of SSTR2 gene has antitumor effects on experimental pancreatic cancer. Restoration of SSTR2 gene expression through gene transfer in vivo might be a potential gene therapy strategy for human pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy / methods*
  • Humans
  • Immunohistochemistry
  • Injections, Intralesional
  • Mice
  • Mice, Nude
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Receptors, Somatostatin / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • Receptors, Somatostatin
  • Sstr2 protein, mouse