Everolimus combined with cisplatin has a potential role in treatment of urothelial bladder cancer - 07/03/13

Doi : 10.1016/j.biopha.2012.11.007

Rosário Pinto-Leite ^a,^{^{1
Tel.: +35 12 59 30 05 00; fax: +35 12 59 30 03 47.}} , Regina Arantes-Rodrigues ^b,^{^{2
Tel.: +35 19 35 60 77 83; fax: +35 12 59 35 04 80.}} , Carlos Palmeira ^c,^d,^{^{3
Tel.: +35 12 25 08 40 00; fax: +35 12 25 08 40 01.}} , Bruno Colaço ^b,^{^{4
Tel.: +35 19 39 45 37 04; fax: +35 12 59 35 04 80.}} , Carlos Lopes ^e,^{^{5
Tel.: +35 12 25 51 11 94; fax: +35 12 25 51 11 94.}} , Aura Colaço ^b,^{^{6
Tel.: +35 19 34 28 70 04; fax: +35 12 59 35 04 80.}} , Céu Costa ^d,^{^{7
Tel.: +35 12 25 07 46 30; fax: +35 12 25 07 46 37.}} , Vítor Moreira da Silva ^f,^{^{3
Tel.: +35 12 25 08 40 00; fax: +35 12 25 08 40 01.}} , Paula Oliveira ^b,^⁎ , Lúcio Santos ^c,^{^{3
Tel.: +35 12 25 08 40 00; fax: +35 12 25 08 40 01.}}
^a Genetic Service, Cytogenetic Laboratory, Hospital Center of Trás-os-Montes and Alto Douro, 5000-508, Vila Real, Portugal
^b Department of Veterinary Sciences, CECAV, University of Trás-os-Montes and Alto Douro, 5001-801, Vila Real, Portugal
^c Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-072, Porto, Portugal
^d Health Faculty, Fernando Pessoa University, 4200-1250, Porto, Portugal
^e Department of Molecular Biology and Immunology, ICBAS, Porto University, 4099-003, Porto, Portugal
^f Department of Urology, Portuguese Institute of Oncology, 4200-072, Porto, Portugal

^⁎Corresponding author. Tel.: +35 19 66 47 30 62; fax: +35 12 59 35 04 80.

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Abstract

Cisplatin (CDDP)-based chemotherapy is a commonly treatment for advanced urothelial carcinoma. However, episodes of cisplatin resistance have been referenced. Recently it has been reported that everolimus (RAD001) could have an important role to play in bladder-cancer treatment and that mTOR inhibitors may restore chemosensitivity in resistant tumours. The aim of this study was to assess RAD001 in vitro ability to enhance CDDP cytotoxicity in three human bladder-cancer cell lines. Over the course of 72h, the cells were exposed to different concentrations of CDDP and RAD001, isolated or combined. Treatment with CDDP statistically (P<0.05) decreased cell proliferation in cell lines in a dose-dependent manner. The anti-proliferative activity of CDDP used in combination with RAD001 was statistically significant (P<0.05) in the cell lines at all concentrations tested. RAD001 had a therapeutic effect when used in combination with CDDP and could therefore be a useful anti-cancer drug combination for patients with bladder cancer.

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Keywords : Bladder-cancer cell lines, Cisplatin, Everolimus

Plan

Introduction

Materials and methods

Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay (TUNEL)

Immunocytochemistry

Statistical analysis

Results

Cytotoxic effects of CDDP and RAD001 against HT1376, T24 and 5637 cells

Cell-cycle analysis

TUNEL assay

Immunocytochemistry analysis

Discussion and conclusion

Disclosure of interest

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Vol 67 - N° 2

P. 116-121 - mars 2013 Retour au numéro

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Everolimus combined with cisplatin has a potential role in treatment of urothelial bladder cancer - 07/03/13

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