title: Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.
abstract: 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.
authors.affiliation: Michael E DeBakey Department of Surgery, Molecular Surgeon Research Center, Baylor College of Medicine, Houston, Texas, USA. minli@bcm.edu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: F Charles
authors.initials: FC
authors.lastname: Brunicardi
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
authors.forename: William E
authors.initials: WE
authors.lastname: Fisher
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1