Meloxicam synergistically enhances the in vitro effects of sunitinib malate on bladder-cancer cells

Arantes‐Rodrigues, Regina; Pinto‐Leite, Rosário; Gonçalves, Lio; Gaivão, Isabel; Colaço, Aura; Oliveira, Paula A.; Santos, Lúcio Lara

doi:10.2478/v10136-012-0034-7

Cited by 3 publications

(3 citation statements)

References 50 publications

(31 reference statements)

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“…The treatment of HT1376, T24, and 5637 urinary bladder-cancer cell lines with cisplatin and sunitinib malate, in isolation, significantly ( P < 0.05) reduced cell viability in a dose-dependent manner as already reported in our previous studies [ 7 , 20 ]. Similar results were described on 5637, J82, HT1197, and 253J urinary bladder-cancer cell lines [ 21 ], as well as on A2780 and OVCAR3 ovarian cancer cells [ 22 ] when exposed to cisplatin in isolation.…”

Section: Discussionsupporting

confidence: 83%

“…Thus, novel targeted therapies are sorely required to further improve the effectiveness of urinary bladder cancer chemotherapy. Preclinical models play a crucial role in this setting [ 17 ] and urinary bladder-cancer cell lines have been invaluable research tools to evaluate the efficacy of new drugs [ 18 – 20 ]. In the present study, we investigated if sunitinib malate could strengthen cisplatin cytotoxicity, using as in vitro models three human urinary bladder-cancer cell lines representative of human urinary bladder tumors: one nonmuscle invasive cell line (5637) and two muscle-invasive cell lines (T24 and HT1376).…”

Section: Discussionmentioning

confidence: 99%

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Synergistic Effect between Cisplatin and Sunitinib Malate on Human Urinary Bladder-Cancer Cell Lines

Arantes‐Rodrigues

Pinto‐Leite

Gonçalves

et al. 2013

BioMed Research International

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The aim of this paper is to analyse sunitinib malate in vitro ability to enhance cisplatin cytotoxicity in T24, 5637, and HT1376 human urinary bladder-cancer cell lines. Cells were treated with cisplatin (3, 6, 13, and 18 μM) and sunitinib malate (1, 2, 4, 6, and 20 μM), either in isolation or combined, over the course of 72 hours. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, acridine orange, and monodansylcadaverine staining and flow cytometry were performed. The combination index (CI) was calculated based on the Chou and Talalay method. In isolation, cisplatin and sunitinib malate statistically (P < 0.05) decrease cell viability in all cell lines in a dose-dependent manner, with the presence of autophagic vacuoles. A cell cycle arrest in early S-phase and in G0/G1-phase was also found after exposure to cisplatin and sunitinib malate, in isolation, respectively. Treatment of urinary bladder-cancer cells with a combination of cisplatin and sunitinib malate showed a synergistic effect (CI < 1). Autophagy and apoptosis studies showed a greater incidence when the combined treatment was put into use. This hints at the possibility of a new combined therapeutic approach. If confirmed in vivo, this conjugation may provide a means of new perspectives in muscle-invasive urinary bladder cancer treatment.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Synergistic Effect between Cisplatin and Sunitinib Malate on Human Urinary Bladder-Cancer Cell Lines

Arantes‐Rodrigues

Pinto‐Leite

Gonçalves

et al. 2013

BioMed Research International

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“…The combination of either aspirin or celecoxib with 5-fluorouracil (5-FU) was capable of improving chemosensitivity in chemorefractory colorectal cancer cells in vitro, but a synergistic effect with 5-FU could only be demonstrated with celecoxib (Rahman et al, 2012). Treatment of bladder cancer cells with a combination of sunitinib malate and meloxicam showed a synergistic effect, and there was an increase in the number of autophagic vacuoles and early apoptotic cells when the combined treatment was employed (Arantes-Rodrigues et al, 2013). In accordance with these results, we showed here that the treatment of human lung cancer A549 xenografts in nude mice with a combination of doxorubicin and meloxicam inhibited tumor growth both in vitro and in vivo more efficiently than doxorubicin treatment alone ( Figure 1 and Table 1).…”

Section: Discussionmentioning

confidence: 99%

Meloxicam increases intracellular accumulation of doxorubicin via downregulation of multidrug resistance-associated protein 1 (MRP1) in A549 cells

Chen

Zhang

2015

Genet. Mol. Res.

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ABSTRACT. It has been suggested that selected COX inhibitors can overcome multidrug resistance through the inhibition of ATP-binding cassette-transporter proteins thereby enhancing the inhibitory effect of doxorubicin on human tumor growth and promoting the actions of cytostatics. However, their effect on lung cancer and the molecular mechanisms involved in the overcoming of multidrug resistance are unclear. In the present study, the ability of meloxicam, a COX-2-specific inhibitor to enhance doxorubicin-mediated inhibition was investigated in human A549 lung cancer in vivo and in vitro. In order to unravel the molecular mechanisms involved in doxorubicin accumulation, we measured the levels of multidrug resistance-associated protein (MRP)-transporter protein activity and expression by western blotting, since this has been implicated in meloxicam action as well as in chemoresistance. We found that, in A549 cells, meloxicam could increase intracellular accumulation of doxorubicin, a substrate for MRP, through inhibition of cellular export. Western blot analysis indicated that meloxicam reduced 14549 COX-2 inhibitor as a lung cancer therapeutic ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 14548-14560 (2015) the expression of MRP1 and MRP4. The results reported in the present study demonstrate for the first time that the specific COX-2 inhibitor meloxicam can increase the intracellular accumulation of doxorubicin and enhance doxorubicin-induced cytotoxicity in A549 cancer cells by reducing the expression of MRP1 and MRP4.

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Effects of Naproxen on Cell Proliferation and Genotoxicity in MG-63 Osteosarcoma Cell Line

Correia

Arantes‐Rodrigues

Pinto‐Leite

et al. 2014

Journal of Toxicology and Environmental Health, Part A

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The purpose of this study was to determine the efficacy of naproxen, a nonsteroidal anti-inflammatory drug, on the MG-63 human osteosarcoma cell line. MG-63 cells were exposed to naproxen in a wide range of concentrations of 0.03, 0.05, 0.1, 0.42, 0.83, and 1.67 mg/ml for 72 h. The activity of naproxen was assessed by the following assays: cell morphology; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay; comet assay; and acridine orange and monodansylcadaverine (MDC) staining. Naproxen exerted a significant inhibitory effect on MG-63 cell proliferation, in a concentration-dependent manner, in all treatment groups compared with untreated cells. An increase in frequency of DNA damage, apoptotic bodies, apoptotic cells, and autophagic vacuoles was observed in MG-63-treated cells. Although future studies are needed, these findings suggest that naproxen may lead to improvements in treatment of patients with osteosarcoma.

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Meloxicam synergistically enhances the in vitro effects of sunitinib malate on bladder-cancer cells

Cited by 3 publications

References 50 publications

Synergistic Effect between Cisplatin and Sunitinib Malate on Human Urinary Bladder-Cancer Cell Lines

Synergistic Effect between Cisplatin and Sunitinib Malate on Human Urinary Bladder-Cancer Cell Lines

Meloxicam increases intracellular accumulation of doxorubicin via downregulation of multidrug resistance-associated protein 1 (MRP1) in A549 cells

Effects of Naproxen on Cell Proliferation and Genotoxicity in MG-63 Osteosarcoma Cell Line

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