Inhibition of Epithelial-Mesenchymal Transition and Migration in Cisplatin-resistant Cancer Through Combined Treatment With Cisplatin and SH003.

IF 1.6 4区 医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-10-01 DOI:10.21873/anticanres.17265
Hyeong Sim Choi, Jeong-Kui Ku, Seong-Gyu Ko, Pil-Young Yun
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Abstract

Background/aim: This study investigated the synergistic effects of combining cisplatin and SH003 treatment on the viability, apoptosis, cytotoxicity, migration and epithelial-mesenchymal transition (EMT) in cisplatin-resistant cancer cell lines YD-8/CIS, YD-9/CIS and YD-38/CIS.

Materials and methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell viability, while trypan blue exclusion assay was used to evaluate cytotoxicity. Flow cytometry and western blot analysis measured apoptotic cell death. Wound-healing assays evaluated cell migration and EMT markers. Combination index (CI) plots were used to evaluate the combinatory effects of the treatment.

Results: Combination therapy significantly reduced cell viability more effectively than each agent alone, as demonstrated by the MTT assay, with CI plots confirming notable synergism. Trypan blue exclusion assays indicated increased cell death and cytotoxicity in combination treatment than in both monotherapies, although the increase was not significant. Flow cytometry and western blot analysis revealed no significant synergistic effect on apoptotic cell death. However, wound-healing assays revealed that the combination of cisplatin and SH003 significantly inhibited cell migration and regulated EMT markers, indicating the potential reversal of EMT.

Conclusion: Combining cisplatin and SH003 therapy may potentially be a more effective strategy for treating cisplatin-resistant cancer by increasing cytotoxicity and inhibiting metastasis. Further research is required to elucidate the underlying mechanisms and evaluate the in vivo efficacy of this combination therapy.

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通过顺铂和 SH003 联合治疗抑制顺铂耐药癌症的上皮-间质转化和迁移
背景/目的:本研究探讨了顺铂和SH003联合治疗对顺铂耐药癌细胞株YD-8/CIS、YD-9/CIS和YD-38/CIS的活力、凋亡、细胞毒性、迁移和上皮-间质转化(EMT)的协同作用:3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑(MTT)检测法用于评估细胞活力,胰蓝排除法用于评估细胞毒性。流式细胞术和 Western 印迹分析测定了细胞凋亡情况。伤口愈合试验评估了细胞迁移和 EMT 标记。联合指数(CI)图用于评估治疗的联合效应:结果:如 MTT 试验所示,联合疗法比单独使用每种药物更有效地降低了细胞活力,CI 图证实了明显的协同作用。胰蓝排除试验表明,与两种单一疗法相比,联合疗法增加了细胞死亡和细胞毒性,但增幅并不明显。流式细胞术和 Western 印迹分析表明,联合疗法对细胞凋亡没有明显的协同作用。然而,伤口愈合试验显示,顺铂和SH003联合用药可明显抑制细胞迁移并调节EMT标记物,这表明联合用药有可能逆转EMT:结论:顺铂和SH003联合治疗可能是治疗顺铂耐药癌症的一种更有效的策略,它能增加细胞毒性并抑制转移。要阐明这种联合疗法的内在机制并评估其体内疗效,还需要进一步的研究。
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来源期刊
Anticancer research
Anticancer research 医学-肿瘤学
CiteScore
3.70
自引率
10.00%
发文量
566
审稿时长
2 months
期刊介绍: ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
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