caveolin-1通過阻斷PI3K/Akt信號的激活抑制胰腺癌細胞增殖_《中國普外基礎與臨床雜志》

作者：

王曉輝 ¹ , 李非 ¹ , 鄭亞民 ¹ , 孫海晨 ² , 劉爽 ²

1.首都醫科大學宣武醫院普外科(北京 100053);;
2.首都醫科大學宣武醫院外科實驗室(北京 100053);

關鍵詞：

Caveolin-1 細胞周期集落形成 Akt

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目的研究caveolin-1對胰腺癌Panc1細胞在體外生長和增殖的影響，并初步探討其機理。方法選用人類胰腺癌Panc1細胞，通過基因轉染技術培育過表達caveolin-1細胞株Panc1/cav-1作為實驗組，空載體細胞株Panc1/vec和親本細胞株Panc1作為對照組。Western blot方法檢測各組細胞內caveolin-1、Akt和pAkt的表達，繪制細胞生長曲線并計算細胞倍增時間，流式細胞儀分析細胞周期，軟瓊脂集落形成實驗檢測細胞增殖克隆的能力。結果①caveolin-1在實驗組細胞中穩定表達，其表達量明顯高于對照組細胞(P lt;0.01)，而對照組的Panc1/vec細胞和Panc1細胞之間差異無統計學意義(P gt;0.05)。②實驗組細胞的生長速度明顯慢于對照組細胞(P lt;0.05)，其倍增時間明顯長于對照組細胞(P lt;0.01)。③細胞周期顯示，實驗組細胞被抑制于G0/G1期(P lt;0.05)，進入S期的細胞比率明顯減少(P lt;0.01)，實驗組細胞的增殖指數較對照組明顯降低(P lt;0.01)。④實驗組細胞在軟瓊脂中形成的集落數目較對照組明顯減少(P lt;0.01)，體積較小。⑤實驗組細胞中Akt表達量與對照組之間差異無統計學意義(P gt;0.05)，而實驗組細胞中p-Akt表達量明顯低于對照組(P lt;0.05)。結論caveolin-1通過抑制PI3K/Akt信號激活抑制Panc1細胞生長和增殖。

引用本文： 王曉輝,李非,鄭亞民,孫海晨,劉爽. caveolin-1通過阻斷PI3K/Akt信號的激活抑制胰腺癌細胞增殖. 中國普外基礎與臨床雜志, 2011, 18(10): 1054-1059. doi: 復制

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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.
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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. 孫備, 陳華. 胰腺癌外科治療的現狀與展望 [J]．中國普外基礎與臨床雜志, 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. 羅紅梅, 唐圣松, 廖端芳, 等. Caveolin1對胃癌細胞系MGC803細胞生長的影響 [J]．世界華人消化雜志, 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.

《中國普外基礎與臨床雜志》

caveolin-1通過阻斷PI3K/Akt信號的激活抑制胰腺癌細胞增殖

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《中國普外基礎與臨床雜志》

caveolin-1通過阻斷PI3K/Akt信號的激活抑制胰腺癌細胞增殖

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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