Repository of Research and Investigative Information

Repository of Research and Investigative Information

Shahid Sadoughi University of Medical Sciences

Cancer Drug Resistance Reduction via Co-treatment with Oxalipla-tin and Nitazoxanide: Targeting the ABC Transporters

(2023) Cancer Drug Resistance Reduction via Co-treatment with Oxalipla-tin and Nitazoxanide: Targeting the ABC Transporters. Current Molecular Medicine. pp. 834-841. ISSN 15665240 (ISSN)

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Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

Abstract

Objects: Shortly after cancer is diagnosed, a phenomenon develops in cancer cells called multidrug resistance (MDR), in which cell sensitivity against anti-cancer drugs is significantly reduced. The present investigation aimed to assess the effects of nita-zoxanide (NTZ), a safe drug, on LS174T/OXP-resistant cells. Methods: In the current in vitro research, the effects of NTZ and oxaliplatin (OXP) on the viability of LS174T and LS174T/OXP cell lines were evaluated through MTT assay. Then, the changes in expression levels of MDR1, MRP1, BCRP, and LRP genes and proteins were measured by RT-qPCR and western blotting methods, respectively. Lastly, the apoptosis status was assessed by annexin V–FITC/PI staining flow cytometry assay. Results: The IC50 values for cells resistant or sensitive to OXP were revealed (11567 nM vs. 1745 nM; p <0.05 for 24 h incubation, and 5161 nM vs. 882.2 nM; p <0.05 for 48 h incubation). Moreover, NTZ plus OXP led to a leftward shift in the cytotoxicity curve (2004 nM; p = 0.007). This co-treatment significantly decreased the expression of all genes and proteins (p <0.05). Finally, the combination of NTZ and OXP induced a significant increase in apoptosis (p <0.001). Conclusion: The data showed that NTZ treatment could increase the sensitivity of LS174T/OXP cell line to the OXP cytotoxic effects. Thus, NTZ may be efficient in redu-cing drug resistance in clinics by means of the negative regulation of ATP-binding cassette (ABC) transporters. However, further studies are necessary to explain the exact mechanisms of NTZ. © 2023 Bentham Science Publishers.

Item Type: Article
Keywords: ABC transporters ATP-binding cassette Colorectal cancer multidrug resistance nitazoxanide oxaliplatin Antineoplastic Agents ATP Binding Cassette Transporter, Subfamily B, Member 1 ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters Cell Line, Tumor Drug Resistance, Multiple Drug Resistance, Neoplasm Multidrug Resistance-Associated Proteins Neoplasm Proteins Neoplasms ABC transporter breast cancer resistance protein lung resistance protein multidrug resistance associated protein 1 multidrug resistance protein 1 antineoplastic agent multidrug resistance associated protein tumor protein apoptosis Article breast cancer cell proliferation cell viability cell viability assay controlled study cytotoxicity down regulation flow cytometry gene expression human human cell IC50 LS174T cell line MTT assay OXP cell line protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction RNA extraction RNA interference upregulation Western blotting drug resistance genetics metabolism neoplasm tumor cell line
Page Range: pp. 834-841
Journal or Publication Title: Current Molecular Medicine
Volume: 23
Number: 8
Identification Number: https://doi.org/10.2174/1566524023666220820154623
ISSN: 15665240 (ISSN)
Depositing User: Mr mahdi sharifi
URI: http://eprints.ssu.ac.ir/id/eprint/31462

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