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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2016

Open Access 01-12-2016 | Research

Maspin enhances cisplatin chemosensitivity in bladder cancer T24 and 5637 cells and correlates with prognosis of muscle-invasive bladder cancer patients receiving cisplatin based neoadjuvant chemotherapy

Authors: Jinbo Chen, Long Wang, Yunhua Tang, Guanghui Gong, Longfei Liu, Minfeng Chen, Zhi Chen, Yu Cui, Chao Li, Xu Cheng, Lin Qi, Xiongbing Zu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

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Abstract

Background

Maspin, a non-inhibitory member of the serine protease inhibitor superfamily, has been characterized as a tumor suppressor gene in multiple cancer types. Chemotherapeutic insensitivity is one of major obstacles to effectively treating muscle invasive bladder cancer (MIBC). This study was conducted to investigate the role and probable mechanism of Maspin enhancing cisplatin chemosensitivity of bladder cancer in vitro and MIBC patients.

Methods

Maspin expression was quantified by qRT-PCR in two MIBC cell lines (T24 and 5637). After successful established Maspin overexpression model by lipidosome transfection, MTT and cell apoptosis assay were used to assess the MIBC’s cisplatin sensitivity. Western blot method was used to test PI3K/ AKT/mTOR signal passway and apoptosis related molecules Caspase3 and Bcl-2. Additionally, we evaluated Maspin expression and prognosis in 62 MIBC cases who underwent cisplatin based neoadjuvant chemotherapy (NACT) using immunohistochemistry.

Result

Upregulate Maspin expression could enhance the chemosensitivity induced by cisplatin in T24 and 5637 cell lines. The cell viability, cloning ability and IC50 were reduced while apoptosis rate was upregulated when cells were transfected Maspin. Phospho(p)-AKT, PI3K, mTOR, and Bcl-2 expression were significantly decreased, whereas Caspase3 was greatly increased in the Maspin group. In the clinic study, there was significant correlation between Maspin expression and overall survival (OS) and progression-free survival (PFS) rate in MIBC patients who received cisplatin based NACT.

Conclusion

Maspin could enhance cisplatin chemosensitivity in T24 and 5637 cell lines. Its expression correlated with prognosis of MIBC patients who received cisplatin based neoadjuvant chemotherapy.
Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
2.
Herr HW. Transurethral resection of muscle-invasive bladder cancer: 10-year outcome. J Clin Oncol. 2001;19(1):89–93.PubMed
3.
Botteman MF, Pashos CL, Redaelli A, Laskin B, Hauser R. The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics. 2003;21:1315–30.CrossRefPubMed
4.
Cookson MS, Herr HW, Zhang ZF, Soloway S, Sogani PC, Fair WR. The treated natural history of high-risk superficial bladder cancer: 15-year outcome. J Urol. 1997;158:62–7.CrossRefPubMed
5.
Gallagher DJ, Milowsky MI, Bajorin DF. Advanced bladder cancer: status of first-line chemotherapy and the search for active agents in the second-line setting. Cancer. 2008;113(6):1284–93.CrossRefPubMed
6.
Witjes JA, Compérat E, Cowan NC, De SM, Gakis G, Lebret T, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol. 2014;65(4):778–92.CrossRefPubMed
7.
Tanji N, Ozawa A, Miura N, Yanagihara Y, Azuma K, Sasaki T, et al. Long-term results of combined chemotherapy with gemcitabine and cisplatin for metastatic urothelial carcinomas. Int J Clin Oncol. 2010;15(4):369–75.CrossRefPubMed
8.
9.
Bodenstine TM, Seftor RE, Khalkhali-Ellis Z, Seftor EA, Pemberton PA, Hendrix MJ. Maspin: molecular mechanisms and therapeutic implications. Cancer Metastasis Rev. 2012;31(3–4):529–51.CrossRefPubMed
10.
Beecken WD, Engl T, Engels K, Blumenberg C, Oppermann E, Camphausen K, et al. Clinical relevance of maspin expression in bladder cancer. World J Urol. 2006;24(3):338–44.CrossRefPubMed
11.
Pawel S, Verena M, Malgorzata GZ, Andrzej W, Irina K, Marek S, et al. Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates. Int J Gynecol Pathol. 2006;25(2):131–9.CrossRef
12.
Triulzi T, Ratti M, Tortoreto M, Cristina G, Piera A, Viola R, et al. Maspin influences response to doxorubicin by changing the tumor microenvironment organization. Int J Cancer. 2014;134(12):2789–97.CrossRefPubMed
13.
Lei KF, Liu BY, Jin XL, Guo Y, Ye M, Zhu ZG. Prognostic value of nuclear maspin expression for adjuvant 5-fluorouracil-based chemotherapy in advanced gastric cancer. Exp Ther Med. 2012;3(6):993–8.PubMedPubMedCentral
14.
Sugimoto S, Maass N, Takimoto Y, Katsuhiko S, Sadatsugu M, Ming Z, et al. Expression and regulation of tumor suppressor gene maspin in human bladder cancer. Cancer Lett. 2004;203(2):209–15.CrossRefPubMed
15.
Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, et al. Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science. 1994;263(5146):526–9.CrossRefPubMed
16.
17.
Lockett J, Yin S, Li X, Meng Y, Sheng S. Tumor suppressive maspin and epithelial homeostasis. J Cell Biochem. 2006;97:651–60.CrossRefPubMed
18.
Kramer MW, Waalkes S, Hennenlotter J, Serth J, Stenzl A, Kuczyk MA, et al. Maspin protein expression correlates with tumor progression in non-muscle invasive bladder cancer. Oncol Lett. 2010;1(4):621–6.PubMedPubMedCentral
19.
Acikalin D, Oner U, Can C, Acikalin MF, Colak E. Predictive value of maspin and Ki-67 expression in transurethral resection specimens in patients with T1 bladder cancer. Tumori. 2012;98(3):344–50.PubMed
20.
Blandamura S, D’Alessandro E, Giacomelli L, Guzzardo V, Battanello W, Repele M, et al. Expression of maspin in papillary Ta/T1 bladder neoplasms. Anticancer Res. 2008;28:471–8.PubMed
21.
Jiang N, Meng Y, Zhang S, Mensah OE, Sheng S. Maspin sensitizes breast carcinoma cells to induced apoptosis. Oncogene. 2002;21:4089–98.CrossRefPubMed
22.
Ben Shachar B, Feldstein O, Hacohen D, Ginsberg D. The tumor suppressor maspin mediates E2F1-induced sensitivity of cancer cells to chemotherapy. Mol Cancer Res. 2010;8:363–372.
23.
24.
Li X, Chen D, Yin S, Meng Y, Yang H, Landis-Piwowar KR, et al. Maspin augments proteasome inhibitor-induced apoptosis in prostate cancer cells. J Cell Physiol. 2007;212:298–306.CrossRefPubMed
25.
26.
Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, et al. Systems biology of cisplatin resistance: past, present and future. Cell Death Dis. 2014;5, e1257.CrossRefPubMedPubMedCentral
27.
Ye L, Bin L, Shiyu T, Lin Q, Xiheng H, Yunbo C, et al. miR-101 suppresses vascular endothelial growth factor C that inhibits migration and invasion and enhances cisplatin chemosensitivity of bladder cancer cells. PloS One. 2015;10(2):e0117809.CrossRef
28.
Nordentoft I, Dyrskjøt L, Bødker JS, Wild PJ, Hartmann A, Bertz S, et al. Increased expression of transcription factor TFAP2 correlates with chemosensitivity in advanced bladder cancer. BMC Cancer. 2011;11:135.CrossRefPubMedPubMedCentral
29.
Yan Z, Jiang J, Li F, Yang W, Xie G, Zhou C, et al. Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin. Oncol Rep. 2015;33(4):1791–8.PubMed
30.
Kavitha R, Edna G, Rakesh S. 5-azacytidine reverses drug resistance in bladder cancer cells. Anticancer Res. 2011;31(11):3757–66.
31.
Zhou H, Tang K, Xiao H, Zeng J, Guan W, Guo X, et al. A panel of eight-miRNA signature as a potential biomarker for predicting survival in bladder cancer. J Exp Clin Cancer Res. 2015;34:53.CrossRefPubMedPubMedCentral
32.
Wu D, Tao J, Xu B, Qing W, Li P, Lu Q, et al. Phosphatidylinositol 3-kinase inhibitor LY294002 suppresses proliferation and sensitizes doxorubicin chemotherapy in bladder cancer cells. Urol Int. 2011;86(1):346–54.CrossRefPubMed
33.
Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ. BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci U S A. 1991;88(16):6961–5.CrossRefPubMedPubMedCentral
34.
Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899–911.CrossRefPubMed
35.
Sun CH, Chang YH, Pan CC. Activation of the PI3K/Akt/mTOR pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder. Histopathology. 2011;58:1054–63.CrossRefPubMed
36.
Yang X, Fraser M, Moll UM, Ajoy B, Tsang BK. Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspase-dependent mitochondrial death pathway. Cancer Res. 2006;66:3126–36.CrossRefPubMed
37.
Liu LZ, Zhou XD, Qian G, Shi X, Fang J, Jiang BH. AKT1 amplification regulates cisplatin resistance in human lung cancer cells through the mammalian target of rapamycin/p70S6K1 pathway. Cancer Res. 2007;67:6325–32.CrossRefPubMed
38.
Sun D, Sawada A, Nakashima M, Kobayashi T, Ogawa O, Matsui Y. MK2206 potentiates cisplatin-induced cytotoxicity and apoptosis through an interaction of inactivated Akt signaling pathway. Urol Oncol. 2015;33(3):111.e17–26.CrossRef
39.
Beltran A, Parikh S, Liu Y, Cuevas BD, Johnson GL, Futscher BW, et al. Re-activation of a dormant tumor suppressor gene maspin by designed transcription factors. Oncogene. 2007;26:2791–8.CrossRefPubMed
40.
Zhang H, Qi F, Cao Y, Zu X, Chen M, Li Z, et al. 5-Aza-2′-deoxycytidine enhances maspin expression and inhibits proliferation, migration, and invasion of the bladder cancer T24 cell line. Cancer Biother Radiopharm. 2013;28:343–50.CrossRefPubMed
41.
Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett. 2008;267:133–64.CrossRefPubMed
42.
Schaefer JS, Zhang M. Targeting maspin in endothelial cells to induce cell apoptosis. Expert Opin Ther Targets. 2006;10(3):401–8.CrossRefPubMed
43.
Watanabe M, Nasu Y, Kashiwakura Y, Nasu Y, Kashiwakura Y, Kusumi N, et al. Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: long-term maspin expression efficiently suppresses tumor growth. Hum Gene Ther. 2005;16(6):699–710.CrossRefPubMed
Metadata
Title
Maspin enhances cisplatin chemosensitivity in bladder cancer T24 and 5637 cells and correlates with prognosis of muscle-invasive bladder cancer patients receiving cisplatin based neoadjuvant chemotherapy
Authors
Jinbo Chen
Long Wang
Yunhua Tang
Guanghui Gong
Longfei Liu
Minfeng Chen
Zhi Chen
Yu Cui
Chao Li
Xu Cheng
Lin Qi
Xiongbing Zu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-015-0282-y

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