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Article

γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition

  • Authors:
    • Yibing Wang
    • Gongxian Wang
    • Xiali Zhang
    • Xiaocheng Zhou
    • Zhihuan Liu
    • Liang Huang
    • Rensheng Liu
    • Bin Lang
    • Xiaoyuan Xu
    • Weipeng Liu
    • Longlong Fu
    • Bin Fu
  • View Affiliations / Copyright

    Affiliations: Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Laboratory Animal Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, School of Health Sciences, Macau, China Polytechnic Institute, Macau SAR 999078, P.R. China, Department of Key Laboratory of System Bio‑Medicine of Jiangxi, Medical College of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
  • Pages: 2821-2827
    |
    Published online on: May 7, 2015
       https://doi.org/10.3892/mmr.2015.3750
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Abstract

A previous study by our group demonstrated that the expression levels of Notch 1 and Jagged 1 in bladder cancer cells was significantly lower compared with those in normal bladder mucosa, while the expression levels of Notch 1 and Jagged 1 in invasive bladder cancer were higher compared with those in superficial bladder cancer. The present study investigated the effect of the Notch signaling pathway on the drug resistance and invasiveness of bladder cancer cells. It was demonstrated that complete inhibition of the Notch signaling pathway induced significant morphological changes and inhibited cell proliferation and migration (P<0.05). Reverse transcription quantitative polymerase chain reaction and western blot analyses revealed that the mRNA and protein expression levels of E‑cadherin were upregulated (P<0.05) and the mRNA and protein expression levels of N‑cadherin, vimentin and α‑smooth muscle actin were downregulated (P<0.05). The present study concluded that complete inhibition of the Notch signaling pathway inhibited cell proliferation and invasion, and reduced drug resistance in bladder cancer cells, a phenomenon which may be associated with the inhibition of the epithelial‑mesenchymal transition.
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1 

Ploeg M, Aben KK and Kiemeney LA: The present and future burden of urinary bladder cancer in the world. World J Urol. 27:289–293. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Floor S, van Staveren WC, Larsimont D, Dumont JE and Maenhaut C: Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating-cancer stem cells: Distinct, overlapping or same populations. Oncogene. 30:4609–4621. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Gomes LR, Terra LF, Sogayar MC and Labriola L: Epithelial-mesenchymal transition: Implications in cancer progression and metastasis. Curr Pharm Biotechnol. 12:1881–1890. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Yao D, Dai C and Peng S: Mechanism of the mesenchymal-epithelial transition and its relationship with metastatic tumor formation. Mol Cancer Res. 9:1608–1620. 2011. View Article : Google Scholar : PubMed/NCBI

5 

McConkey DJ, Choi W, Marquis L, Martin F, Williams MB, Shah J, Svatek R, Das A, Adam L, Kamat A, Siefker-Radtke A and Dinney C: Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev. 28:335–344. 2009. View Article : Google Scholar : PubMed/NCBI

6 

De Craene B and Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 13:97–110. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Yilmaz M and Christofori G: EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 28:15–33. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Shi TP, Ma X, Fu B, Li H, Ai X, Xu H, Ju Z, Wang C, Zhang G, Wang BJ and Zhang X: Expression of Notch signaling in bladder cancer and its relationship with patients’ prognosis. Chin J Exp Surg. 9:1305–1307. 2010.In Chinese.

9 

Wang Z, Li Y, Kong D and Sarkar FH: The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness. Curr Drug Targets. 11:745–751. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Mills RD, Turner WH, Fleischmann A, Markwalder R, Thalmann GN and Studer UE: Pelvic lymph node metastases from bladder cancer: Outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy. J Urol. 166:19–23. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Kamai T, Tsujii T, Arai K, Takagi K, Asami H, Ito Y and Oshima H: Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Clin Cancer Res. 9:2632–2641. 2003.PubMed/NCBI

12 

Ohashi S, Natsuizaka M, Naganuma S, Kagawa S, Kimura S, Itoh H, Kalman RA, Nakagawa M, Darling DS, Basu D, Gimotty PA, et al: A NOTCH3-mediated squamous cell differentiation program limits expansion of EMT-competent cells that express the ZEB transcription factors. Cancer Res. 71:6836–6847. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Espinoza I and Miele L: Notch inhibitors for cancer treatment. Pharmacol Ther. 139:95–110. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Ishida T, Hijioka H, Kume K, Miyawaki A and Nakamura N: Notch signaling induces EMT in OSCC cell lines in a hypoxic environment. Oncol Lett. 6:1201–1206. 2013.PubMed/NCBI

15 

Li Y, Ma J, Qian X, Wu Q, Xia J, Miele L, Sarkar FH and Wang Z: Regulation of EMT by Notch signaling pathway in tumor progression. Curr Cancer Drug Targets. 13:957–962. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Schwanbeck R, Martini S, Bernoth K and Just U: The Notch signaling pathway: Molecular basis of cell context dependency. Eur J Cell Biol. 90:572–581. 2011. View Article : Google Scholar

17 

Borggrefe T and Oswald F: The Notch signaling pathway: Transcriptional regulation at Notch target genes. Cell Mol Life Sci. 66:1631–1646. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Capobianco AJ, Zagouras P, Blaumueller CM, Artavanis-Tsakonas S and Bishop JM: Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2. Mol Cell Biol. 17:6265–6273. 1997.PubMed/NCBI

19 

Acloque H, Adams MS, Fishwick K, Bronner-Fraser M and Nieto MA: Epithelial-mesenchymal transitions: The importance of changing cell state in development and disease. J Clin Invest. 119:1438–1449. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Shun XD and Wang HZ: Research progress in bladder cancer markers and its detection met hods. J Mod Urol. 17:319–321. 2012.

21 

Gallahan D, Kozak C and Callahan R: A new common integration region (int-3) for mouse mammary tumor virus on mouse chromosome 17. J Virol. 61:218–220. 1987.PubMed/NCBI

22 

Joshi I, Minter LM, Telfer J, Demarest RM, Capobianco AJ, Aster JC, Sicinski P, Fauq A, Golde TE and Osborne BA: Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Blood. 113:1689–1698. 2009. View Article : Google Scholar :

23 

Shi TP, Xu H, Wei JF, Ai X, Ma X, Wang BJ, Ju ZH, Zhang GX, Wang C, Wu ZQ, Zhang X, et al: Association of low expression of notch-1 and jagged-1 in human papillary bladder cancer and shorter survival. J Urol. 180:361–366. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Meng F and Wu G: The rejuvenated scenario of epithelial-mesenchymal transition (EMT) and cancer metastasis. Cancer Metastasis Rev. 31:455–467. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Grego-Bessa J, Díez J, Timmerman L and de la Pompa JL: Notch and epithelial-mesenchyme transition in development and tumor progression: Another turn of the screw. Cell Cycle. 3:718–721. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Leong KG, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I and Karsan A: Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J Exp Med. 204:2935–2948. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Niessen K, Fu Y, Chang L, Hoodless PA, McFadden D and Karsan A: Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J Cell Biol. 182:315–325. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Sabbah M, Emami S, Redeuilh G, Julien S, Prevost G, Zimber A, Ouelaa R, Bracke M, De Wever O and Gespach C: Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist Updat. 11:123–151. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Shah AN, Summy JM, Zhang J, Park SI, Parikh NU and Gallick GE: Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol. 14:3629–3637. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Wang Z, Li Y, Kong D, Banerjee S, Ahmad A, Azmi AS, Ali S, Abbruzzese JL, Gallick GE and Sarkar FH: Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res. 69:2400–2407. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Wang G, Zhang X, Zhou X, Liu Z, Huang L, Liu R, Lang B, Xu X, Liu W, Liu W, et al: γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition. Mol Med Rep 12: 2821-2827, 2015.
APA
Wang, Y., Wang, G., Zhang, X., Zhou, X., Liu, Z., Huang, L. ... Fu, B. (2015). γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition. Molecular Medicine Reports, 12, 2821-2827. https://doi.org/10.3892/mmr.2015.3750
MLA
Wang, Y., Wang, G., Zhang, X., Zhou, X., Liu, Z., Huang, L., Liu, R., Lang, B., Xu, X., Liu, W., Fu, L., Fu, B."γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition". Molecular Medicine Reports 12.2 (2015): 2821-2827.
Chicago
Wang, Y., Wang, G., Zhang, X., Zhou, X., Liu, Z., Huang, L., Liu, R., Lang, B., Xu, X., Liu, W., Fu, L., Fu, B."γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition". Molecular Medicine Reports 12, no. 2 (2015): 2821-2827. https://doi.org/10.3892/mmr.2015.3750
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Wang G, Zhang X, Zhou X, Liu Z, Huang L, Liu R, Lang B, Xu X, Liu W, Liu W, et al: γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition. Mol Med Rep 12: 2821-2827, 2015.
APA
Wang, Y., Wang, G., Zhang, X., Zhou, X., Liu, Z., Huang, L. ... Fu, B. (2015). γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition. Molecular Medicine Reports, 12, 2821-2827. https://doi.org/10.3892/mmr.2015.3750
MLA
Wang, Y., Wang, G., Zhang, X., Zhou, X., Liu, Z., Huang, L., Liu, R., Lang, B., Xu, X., Liu, W., Fu, L., Fu, B."γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition". Molecular Medicine Reports 12.2 (2015): 2821-2827.
Chicago
Wang, Y., Wang, G., Zhang, X., Zhou, X., Liu, Z., Huang, L., Liu, R., Lang, B., Xu, X., Liu, W., Fu, L., Fu, B."γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition". Molecular Medicine Reports 12, no. 2 (2015): 2821-2827. https://doi.org/10.3892/mmr.2015.3750
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