Resistance Improvement and Sensitivity Enhancement of Cancer Therapy by a Novel Antitumor Candidate onto A2780 CP and A2780 S Cell Lines.

IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Reports of Biochemistry and Molecular Biology Pub Date : 2023-10-01 DOI:10.61186/rbmb.12.3.374
Sariyeh Mohammadi Hadloo, Homa Mohseni Kouchesfahani, Ali Khanlarkhani, Maryam Saeidifar
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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.

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一种新型抗肿瘤候选药物对 A2780 CP 和 A2780 S 细胞株抗药性的改善和癌症治疗敏感性的提高
背景:为克服顺铂耐药性,研究了一种新型抗肿瘤药物对顺铂敏感和耐药的两种卵巢癌细胞系的细胞毒性:方法:采用 MTT 法和流式细胞术评估新型水溶性钯(II)复合物 [Pd(bpy)(pyr-dtc)]NO3 (PBPD) 对顺铂敏感和顺铂耐药卵巢癌细胞系的细胞毒性。此外,还使用实时 PCR 评估了耐药基因分化簇 99(CD99)、信号转导和激活转录 3(STAT3)、八聚体结合转录因子 4(OCT4)和多药耐药突变 1(MDR1)的表达变化:结果:耐药细胞中 PBPD 的 IC50 值高于敏感细胞。此外,与耐药细胞相比,PBPD 对敏感细胞的杀伤力更大,细胞存活率随时间推移而降低。流式细胞术显示,PBPD 在促使抗性细胞凋亡的同时,也增加了抗性细胞的存活数量。另一方面,PBPD 对活体细胞群的影响更大,使敏感细胞群急剧转向凋亡和坏死。此外,基因表达分析表明,用顺铂处理敏感细胞和耐药细胞时,所有耐药基因都比对照组显著增加。与 OCT4 相反,与对照组相比,用 PBPD 处理的敏感细胞中 MDR1、STAT3 和 CD99 抗性基因没有明显升高。因此,用 PBPD 处理的耐药细胞中耐药基因的表达量低于顺铂:因此,PBPD是一种治疗CDDP耐药卵巢癌的有前途的抗癌药物。
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来源期刊
Reports of Biochemistry and Molecular Biology
Reports of Biochemistry and Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.80
自引率
23.50%
发文量
60
审稿时长
10 weeks
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.
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