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


CONCLUSIONS
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.
Du
Zhi-Yong
ZY
Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. ryqin@tjh.tjmu.edu.cn
Qin
Ren-Yi
RY
Xia
Wei
W
Tian
Rui
R
Kumar
Manoj
M
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D017481:Receptors, Somatostatin / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D017481:Receptors, Somatostatin; C492049:Sstr2 protein, mouse