Sariyeh Mohammadi Hadloo, Homa Mohseni Kouchesfahani, Ali Khanlarkhani, Maryam Saeidifar
{"title":"Resistance Improvement and Sensitivity Enhancement of Cancer Therapy by a Novel Antitumor Candidate onto A2780 CP and A2780 S Cell Lines.","authors":"Sariyeh Mohammadi Hadloo, Homa Mohseni Kouchesfahani, Ali Khanlarkhani, Maryam Saeidifar","doi":"10.61186/rbmb.12.3.374","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>To overcome cisplatin resistance, the cytotoxicity of a novel antitumor agent on two ovarian cancer cell lines sensitive and resistant to cisplatin was investigated.</p><p><strong>Methods: </strong>MTT assay and flow cytometry were performed to assess the cytotoxicity of a novel water-soluble Pd (II) complex, [Pd(bpy)(pyr-dtc)]NO<sub>3</sub> (PBPD), on cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. Furthermore, variations in the expression of drug resistance gene cluster of differentiation 99 (CD99), signal transducer and activator of transcription 3 (STAT3), octamer-binding transcription factor 4 (OCT4), and multidrug resistance mutation 1 (MDR1) were evaluated using Real-Time PCR.</p><p><strong>Results: </strong>The IC50 values of PBPD in resistant cells were higher than those in sensitive cells. Furthermore, PBPD has a deadlier effect on sensitive cells compared to resistant cells, and the cell survival rate is reduced over time. Flow cytometry revealed that PBPD enhanced the population of living-resistant cells while driving them to apoptosis. PBPD, on the other hand, has a greater effect on the living cell population and has dramatically shifted the population toward apoptosis and necrosis in the sensitive cells. Furthermore, gene expression analysis showed that when sensitive and resistant cells were treated with cisplatin, all resistance genes increased significantly relative to the control. In contrast to OCT4, MDR1, STAT3, and CD99 resistance genes were not significantly elevated in sensitive cells treated with PBPD compared to the control. Thus, the expression of resistance genes in resistant cells treated with PBPD was lower than cisplatin.</p><p><strong>Conclusions: </strong>As a result, PBPD is a promising anticancer agent for CDDP-resistant ovarian cancer.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"12 3","pages":"374-385"},"PeriodicalIF":1.6000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11015932/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reports of Biochemistry and Molecular Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.61186/rbmb.12.3.374","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: To overcome cisplatin resistance, the cytotoxicity of a novel antitumor agent on two ovarian cancer cell lines sensitive and resistant to cisplatin was investigated.
Methods: MTT assay and flow cytometry were performed to assess the cytotoxicity of a novel water-soluble Pd (II) complex, [Pd(bpy)(pyr-dtc)]NO3 (PBPD), on cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. Furthermore, variations in the expression of drug resistance gene cluster of differentiation 99 (CD99), signal transducer and activator of transcription 3 (STAT3), octamer-binding transcription factor 4 (OCT4), and multidrug resistance mutation 1 (MDR1) were evaluated using Real-Time PCR.
Results: The IC50 values of PBPD in resistant cells were higher than those in sensitive cells. Furthermore, PBPD has a deadlier effect on sensitive cells compared to resistant cells, and the cell survival rate is reduced over time. Flow cytometry revealed that PBPD enhanced the population of living-resistant cells while driving them to apoptosis. PBPD, on the other hand, has a greater effect on the living cell population and has dramatically shifted the population toward apoptosis and necrosis in the sensitive cells. Furthermore, gene expression analysis showed that when sensitive and resistant cells were treated with cisplatin, all resistance genes increased significantly relative to the control. In contrast to OCT4, MDR1, STAT3, and CD99 resistance genes were not significantly elevated in sensitive cells treated with PBPD compared to the control. Thus, the expression of resistance genes in resistant cells treated with PBPD was lower than cisplatin.
Conclusions: As a result, PBPD is a promising anticancer agent for CDDP-resistant ovarian cancer.
期刊介绍:
The Reports of Biochemistry & Molecular Biology (RBMB) is the official journal of the Varastegan Institute for Medical Sciences and is dedicated to furthering international exchange of medical and biomedical science experience and opinion and a platform for worldwide dissemination. The RBMB is a medical journal that gives special emphasis to biochemical research and molecular biology studies. The Journal invites original and review articles, short communications, reports on experiments and clinical cases, and case reports containing new insights into any aspect of biochemistry and molecular biology that are not published or being considered for publication elsewhere. Publications are accepted in the form of reports of original research, brief communications, case reports, structured reviews, editorials, commentaries, views and perspectives, letters to authors, book reviews, resources, news, and event agenda.