Curr Ther Res Clin Exp. 2010 Aug;71(4):239-51. doi: 10.1016/j.curtheres.2010.08.005.
Effects of lorglumide on growth and invasion of human pancreatic cancer cell line Mia PaCa-2 in vitro through the cholecystokinin-cholecystokinin-1 receptor pathway.
Current therapeutic research, clinical and experimental
Jin Zhou, Zi-Xiang Zhang, De-Chun Li
Affiliations
Affiliations
- General Surgery Department, The First Affiliated Hospital of Soochow University, Suzhou, China.
PMID: 24688146
PMCID: PMC3969616 DOI: 10.1016/j.curtheres.2010.08.005
Abstract
BACKGROUND: Cholecystokinin (CCK) has been found to be a growth stimulant through its special receptor pathway, especially for gastrointestinal malignancies. Although the CCK-1 receptor has been shown to be highly expressed in resected human pancreatic cancer samples, its role is less clear.
OBJECTIVE: The aim of this in vitro study was to investigate the CCK-1 receptor expression and the function of the CCK-CCK-1 receptor pathway in the human pancreatic adenocarcinoma cell line, Mia PaCa-2.
METHODS: The expression of the CCK-1 receptor in Mia PaCa-2 cells was detected by reverse-transcriptase polymerase chain reaction and flow cytometry. CCK-1 receptor agonist CCK-8S (the major transmitter form of CCK) and antagonist lorglumide were cultured respectively with Mia PaCa-2. Three groups were created for this study: CCK-8S group (Mia PaCa-2 cells treated with CCK-8S), lorglumide group (Mia PaCa-2 cells treated with lorglumide), and the control group (Mia PaCa-2 cells alone). Investigators were blinded to group designation. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry were used to detect the cell growth, cell cycle, and apoptosis. Apoptosis index rate was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Cell invasion ability was observed by invasion assay. Expression of matrix metalloproteinase-2 (MMP-2) was measured by Western blotting.
RESULTS: Mia PaCa-2 cells were found to express the CCK-1 receptor. Compared with the control group (70.2% [1.5%]), CCK-8S was associated with significant mean (SD) cell proliferation (85.1% [1.7%]; P = 0.039), and the ratio in the S stage of the cell cycle increased significantly (50.5% [1.7%] vs 42.2% [1.4%]; P = 0.021). CCK-8S was also associated with increased Mia PaCa-2 cell invasion ability (123.8 [1.7] vs 102.1 [5.8]; P = 0.005 vs control). Compared with the control group, lorglumide was associated with significantly inhibited cell growth (52.1% [1.8%]; P = 0.002) and cell invasion (77.6% [1.2%]; P = 0.003). Lorglumide also induced G0/G1 cell cycle arrest and apoptosis (27.1% [3-5%] vs 3-7% [0.6%]; P = 0.003 vs control). The change of invasion ability appeared to be mediated by MMP-2 expression, which was upregulated by CCK-8S and downregulated by lorglumide.
CONCLUSION: The findings of this in vitro study suggest that CCK may exert a trophic action on the Mia PaCa-2 cell line, while lorglumide inhibited the cell growth and invasion.
Keywords: CCK-1 receptor; MMP-2; apoptosis; cholecystokinin; pancreatic cancer
References
- Cancer Lett. 2005 May 10;222(1):95-105 - PubMed
- N Engl J Med. 2009 May 28;360(22):2366; author reply 2366-7 - PubMed
- Chin Med J (Engl). 2008 Oct 20;121(20):2031-6 - PubMed
- Curr Top Med Chem. 2007;7(12):1232-8 - PubMed
- Cancer Chemother Pharmacol. 2008 Apr;61(5):883-92 - PubMed
- Curr Top Med Chem. 2007;7(12):1239-42 - PubMed
- Br J Pharmacol. 2005 Feb;144(3):338-48 - PubMed
- J Endocrinol. 1976 May;69(2):299-325 - PubMed
- Brain Res. 2006 Oct 30;1117(1):109-17 - PubMed
- Endocr Rev. 2003 Aug;24(4):389-427 - PubMed
- Mol Cancer Ther. 2006 Apr;5(4):787-96 - PubMed
- Clin Cancer Res. 2000 Jul;6(7):2726-34 - PubMed
- Am J Clin Nutr. 1973 Mar;26(3):291-310 - PubMed
- Ann Oncol. 1999;10 Suppl 4:131-5 - PubMed
- J Gastrointest Surg. 1999 Mar-Apr;3(2):134-40 - PubMed
- Curr Opin Pharmacol. 2007 Dec;7(6):583-92 - PubMed
- Oncology. 2006;71(1-2):61-8 - PubMed
- Cancer Lett. 2006 May 8;236(1):58-63 - PubMed
- Arch Surg. 2008 Jan;143(1):75-83; discussion 83 - PubMed
- J Clin Oncol. 2009 May 1;27(13):2269-77 - PubMed
- J Nucl Med. 2005 Oct;46(10):1727-36 - PubMed
- J Biol Chem. 2005 Mar 18;280(11):10664-74 - PubMed
- Oncogene. 2006 Jul 27;25(32):4421-8 - PubMed
- Biol Pharm Bull. 2010;33(2):216-22 - PubMed
- Toxicol Pathol. 2007 Jun;35(4):495-516 - PubMed
- Exp Oncol. 2006 Jun;28(2):136-40 - PubMed
- J Pineal Res. 2005 Oct;39(3):243-50 - PubMed
- Curr Opin Urol. 2009 May;19(3):315-21 - PubMed
- Int J Oncol. 2006 Dec;29(6):1429-35 - PubMed
- Am J Physiol. 1998 Apr;274(4 Pt 1):G607-13 - PubMed
- Endocr Relat Cancer. 2009 Sep;16(3):715-31 - PubMed
- Ann Oncol. 2008 Jul;19(7):1224-1230 - PubMed
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