Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.
Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer.
Li
Min
M
Michael E DeBakey Department of Surgery, Molecular Surgeon Research Center, Baylor College of Medicine, Houston, Texas, USA. minli@bcm.edu
Wang
Xiaochi
X
Li
Wei
W
Li
Fei
F
Yang
Hui
H
Wang
Hao
H
Brunicardi
F Charles
FC
Chen
Changyi
C
Yao
Qizhi
Q
Fisher
William E
WE
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1