Transfection of SSTR-1 and SSTR-2 Inhibits Panc-1 Cell Proliferation and Renders Panc-1 Cells Responsive to Somatostatin Analogue - 21/08/11
, †, Rongxin Zhang, PhD †, Fei Li, MS †, Hao Wang, PhD †, Hee Joon Kim, BA §, Lauren Becnel, BA ‡, Qizhi Yao, MD, PhD ‡, Changyi Chen, MD, PhD †, William E. Fisher, MD †, ⁎ : FACS Elkins Pancreas Center, Houston, TX Correspondence address: William E Fisher, MD, Elkins Pancreas Center and Michael E DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin St, Smith Tower 1661, Houston, TX 77030Résumé |
Background |
Somatostatin inhibits cell proliferation through interaction with its cellular receptor, somatostatin receptors (SSTRs). We have previously demonstrated that overexpression of individual SSTR-1 or SSTR-2 genes in receptor-negative pancreatic cancer cells inhibited cell proliferation. We hypothesize that reintroduction of SSTR genes back into pancreatic cancer cells might be an effective gene therapy strategy for pancreatic cancer.
Study design |
We transfected human pancreatic cancer cell line (Panc-1) with human SSTR-1 and SSTR-2 genes and examined the expression by real-time reverse transcriptase-polymerase chain reaction and immunofluorescence. Panc-1 cell proliferation was determined by [3H]-thymidine incorporation assay. Activation of phosphorylated c-Jun N-terminal protein kinase (JNK) and cytokine secretion after SSTR-1 and SSTR-2 transfection were detected by Bio-Plex 4-plex phosphoprotein assay and cytokine assay.
Results |
Panc-1 cells did not express SSTR-1 or SSTR-2, although Panc-1 cells transfected with SSTR-1 and SSTR-2 genes showed a significant amount of SSTR expression. Cell growth rate in Panc-1 cells transfected with SSTR-1 and SSTR-2 was inhibited about 41%, and the cell proliferation of Panc-1 expressing SSTR-1 and SSTR-2 was further reduced about 12% on treatment with somatostatin analogue as compared with the control group. SSTR-1 and SSTR-2 cotransfected Panc-1 cells activated phosphorylation of JNK and increased secretion of interferon-γ and interleukin-5.
Conclusions |
These findings suggest, for the first time, a synergistic inhibitory effect of multiple SSTRs in response to a somatostatin analogue in Panc-1 cells. These studies may improve our understanding of the mechanism by which SSTR inhibits cell growth and lead to novel gene therapies for pancreatic cancer.
Le texte complet de cet article est disponible en PDF.Abbreviations and Acronyms : EGF, IFN-γ, IL, JNK, Panc-1, RT-PCR, SSTR
Plan
| Competing Interests Declared: None. |
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| Supported by National Institutes of Health Grants K08 CA85822 (WEF) and the Methodist Hospital Foundation Grant 39935 (ML). |
Vol 201 - N° 4
P. 571-578 - octobre 2005 Retour au numéro
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