Caveolin-1 Inhibits Proliferation of Pancreatic Carcinoma Cells Through Suppressing Activation of PI3K/Akt Signaling Pathway_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Xiaohui ¹ , LI Fei ¹ , ZHENG Yamin ¹ , SUN Haichen ² , LIU Shuang. ²

1.Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;;
2.Surgical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;

Corresponding author：

Keywords：

Caveolin-1; Cell cycle; Colony formation; Akt

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ObjectiveTo investigate the effect and mechanism of caveolion-1 on the growth and proliferation of human pancreatic carcinoma cell Panc1, in vitro. MethodsThe plasmid pCI-neo-cav-1 and its corresponding empty vector (pCI-neo) were transfected into Panc1 cell line (study group and control group, respectively). Expressions of caveolin-1, Akt, and Aktphosphate (p-Akt) were determined in transfectants by Western blot analysis. The cell growth curve was drawn and the double time was calculated in each group, and the cell cycle was analyzed by flow cytometry. The colony formation ability of tumor cells was detected by anchorageindependent growth assay. ResultsCaveolin-1 expression was up-regulated (P lt;0.01) and the growth of Panc1 cell was inhibited significantly (P lt;0.01) in the study group comparing with the control group. Caveolin-1 overexpression inhibited proliferation of Panc1 cell by arresting the cell cycle in the G0/G1 phase (P lt;0.05), the rate of S phase in the study group was lower than that of the control group (P lt;0.01). Proliferation index of the study group was also lower than that of the control group (P lt;0.01). Caveolin-1 overexpression reduced the capacity of the cells to form colonies in soft agar (P lt;0.01). p-Akt protein was reduced in the study group as compared with the control group (P lt;0.05). ConclusionCaveolin-1 can function as a cancer suppressor through inhibiting the activation of PI3K/Akt signaling pathway in Panc1 cell.

Citation： WANG Xiaohui,LI Fei,ZHENG Yamin,SUN Haichen,LIU Shuang.. Caveolin-1 Inhibits Proliferation of Pancreatic Carcinoma Cells Through Suppressing Activation of PI3K/Akt Signaling Pathway. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(10): 1054-1059. doi: Copy

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11.	Wu P, Wang X, Li F, et al. Growth suppression of MCF7 cancer cellderived xenografts in nude mice by caveolin1 [J]. Biochem Biophys Res Commun, 2008, 376(1): 215220.
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14.	Fang K, Fu W, Beardsley AR, et al. Overexpression of caveolin1 inhibits endothelial cell proliferation by arresting the cell cycle at G0/G1 phase [J]. Cell Cycle, 2007, 6(2): 199204.
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17.	Liao WX, Feng L, Zhang H, et al. Compartmentalizing VEGFinduced ERK2/1 signaling in placental artery endothelial cell caveolae: a paradoxical role of caveolin1 in placental angiogenesis in vitro [J]. Mol Endocrinol, 2009, 23(9), 14281444.
18.	Engelman JA, Wykoff CC, Yasuhara S, et al. Recombinant expression of caveolin1 in oncogenically transformed cells abrogates anchorageindependent growth [J]. J Biol Chem, 1997, 272(26): 1637416381.
19.	Han F, Zhu HG. Caveolin1 regulating the invasion and expression of matrix metalloproteinase (MMPs) in pancreatic carcinoma cells [J]. J Surg Res, 2010, 159(1): 443450.
20.	Cantley LC. The phosphoinositide 3kinase pathway [J]. Science, 2002, 296(5573): 16551657.
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22.	He X, Wang Y, Zhu J, et al. Resveratrol enhances the antitumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycininduced AKT signaling [J]. Cancer Lett, 2011, 301(2): 168176.
23.	Cao P, Maira SM, Garcíaecheverría C, et al. Activity of a novel,dual PI3kinase/mTOR inhibitor NVPBEZ235 against primary human pancreatic cancers grown as orthotopic xenografts [J]. Br J Cancer, 2009, 100(8): 12671276.
24.	Fujiwara M, Izuishi K, Sano T, et al. Modulating effect of the PI3kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells [J]. J Exp Clin Cancer Res, 2008, 27(1): 7684.
25.	Ma J, Sawai H, Matsuo Y, et al. IGF1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF1/PI3K/Akt signaling pathway inpancreatic cancer cells [J]. J Surg Res, 2010, 160(1): 90101.

1. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004 [J]. CA Cancer J Clin, 2004, 54(1): 829.
2. 孙备, 陈华. 胰腺癌外科治疗的现状与展望 [J]．中国普外基础与临床杂志, 2008, 15(8): 547549．.
3. Quest AF, GutierrezPajares JL, Torres VA. Caveolin1: an ambiguous partner in cell signalling and cancer [J]. J Cell Mol Med, 2008, 12(4): 11301150.
4. 罗红梅, 唐圣松, 廖端芳, 等. Caveolin1对胃癌细胞系MGC803细胞生长的影响 [J]．世界华人消化杂志, 2006, 14(15): 14481452.
5. Telang N, Katdare M. Novel cell culture model for prevention of carcinogenic risk in familial adenomatous polyposis syndrome [J]. Oncol Rep, 2009, 21(4): 10171021.
6. Kai W, Diatchenko L, Agoulnik A, et al. Caveolin1 is downregulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene [J]. Am J Pathol, 2001, 159(5): 16351643.
7. Sanna E, Miotti S, Mazzi M, et al. Binding of nuclear caveolin1 to promoter elements of growthassociated genes in ovarian carcinoma cells [J]. Exp Cell Res, 2007, 313(7): 13071317.
8. Murakami S, Miyamoto M, Hida Y, et al. Caveolin1 overexpression is a favourable prognostic factor for patients with extrahepatic bile duct carcinoma [J]. Br J Cancer, 2003, 88(8): 12341238.
9. Gu D, Li H, Wang Z, et al. Caveolin1 inhibits the growth of human laryngeal squamous cell carcinoma and down regulates EGFRMAPKs signaling pathway [J]. Laryngoscope, 2007, 117(10): 17821789.
10. Wu P, Qi BJ, Zhu H, et al. Suppression of staurosporinemediated apoptosis in Hs578T breast cells through inhibition of neutralsphingomyelinase by caveolin1 [J]. Cancer Lett, 2007, 256(1): 6472.
11. Wu P, Wang X, Li F, et al. Growth suppression of MCF7 cancer cellderived xenografts in nude mice by caveolin1 [J]. Biochem Biophys Res Commun, 2008, 376(1): 215220.
12. Tanase CP, Dima S, Mihai M, et al. Caveolin1 overexpression correlates with tumour progression markers in pancreatic ductal adenocarcinoma [J]. J Mol Histol, 2009, 40(1): 2329.
13. Lin M, Divito MM, Merajver SD, et al. Regulation of pancreatic cancer cell migration and invasion by RhoC GTPase and caveolin1 [J]. Mol Cancer, 2005, 4(1): 21.
14. Fang K, Fu W, Beardsley AR, et al. Overexpression of caveolin1 inhibits endothelial cell proliferation by arresting the cell cycle at G0/G1 phase [J]. Cell Cycle, 2007, 6(2): 199204.
15. Qian N, Ueno T. Is dysfunction of caveolin1 a link between systemic sclerosis and breast cancer, opening a window on both etiologies [J]. Arch Med Res, 2010, 41(4):297301.
16. Tahir SA, Park S, Thompson TC. Caveolin1 regulates VEGFstimulated angiogenic activities in prostate cancer and endothelial cells [J]. 2009, 8(23): 22862296.
17. Liao WX, Feng L, Zhang H, et al. Compartmentalizing VEGFinduced ERK2/1 signaling in placental artery endothelial cell caveolae: a paradoxical role of caveolin1 in placental angiogenesis in vitro [J]. Mol Endocrinol, 2009, 23(9), 14281444.
18. Engelman JA, Wykoff CC, Yasuhara S, et al. Recombinant expression of caveolin1 in oncogenically transformed cells abrogates anchorageindependent growth [J]. J Biol Chem, 1997, 272(26): 1637416381.
19. Han F, Zhu HG. Caveolin1 regulating the invasion and expression of matrix metalloproteinase (MMPs) in pancreatic carcinoma cells [J]. J Surg Res, 2010, 159(1): 443450.
20. Cantley LC. The phosphoinositide 3kinase pathway [J]. Science, 2002, 296(5573): 16551657.
21. Boreddy SR, Pramanik KC, Srivastava SK. Pancreatic tumor suppression by benzyl isothiocyanate is associated with inhibition of PI3K/AKT/FOXO pathway [J]. Clin Cancer Res, 2011, 17(7): 17841795.
22. He X, Wang Y, Zhu J, et al. Resveratrol enhances the antitumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycininduced AKT signaling [J]. Cancer Lett, 2011, 301(2): 168176.
23. Cao P, Maira SM, Garcíaecheverría C, et al. Activity of a novel,dual PI3kinase/mTOR inhibitor NVPBEZ235 against primary human pancreatic cancers grown as orthotopic xenografts [J]. Br J Cancer, 2009, 100(8): 12671276.
24. Fujiwara M, Izuishi K, Sano T, et al. Modulating effect of the PI3kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells [J]. J Exp Clin Cancer Res, 2008, 27(1): 7684.
25. Ma J, Sawai H, Matsuo Y, et al. IGF1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF1/PI3K/Akt signaling pathway inpancreatic cancer cells [J]. J Surg Res, 2010, 160(1): 90101.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Caveolin-1 Inhibits Proliferation of Pancreatic Carcinoma Cells Through Suppressing Activation of PI3K/Akt Signaling Pathway

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