福斯塔替尼通过诱导凋亡抑制卵巢癌细胞增殖

IF 1.6 4区 医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17315
Hye Min Lee, Hee Jin Cho, Yul Min Lee, Hyun Jung Kim, Kyun Heo
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引用次数: 0

摘要

背景/目的:卵巢癌死亡率高、预后差,尤其是在晚期,因此仍是一项重大挑战。尽管治疗取得了进展,但耐药性和复发问题依然存在,这凸显了对新的有效疗法的迫切需求。本研究旨在评估福斯塔替尼(一种口服脾脏酪氨酸激酶抑制剂,最初开发用于自身免疫性疾病)作为卵巢癌潜在治疗方法的可能性:采用WST-1细胞增殖试验评估福斯塔替尼对卵巢癌细胞株的影响。通过TUNEL检测、DNA片段分析和流式细胞术评估细胞凋亡。Western印迹分析用于检测凋亡蛋白(包括caspase-3和PARP)的裂解情况,流式细胞术分析细胞周期的变化:结果:福司他替尼治疗可导致卵巢癌细胞生长的剂量和时间依赖性降低,并诱导细胞凋亡,表现为TUNEL阳性细胞增加、DNA片段化以及早期和晚期细胞凋亡的增加。Western 印迹分析显示,凋亡蛋白的裂解增加,包括 caspase-3 和 PARP。流式细胞术还显示细胞周期的亚 G1 期增加,进一步证实了凋亡诱导作用:结论:福司他替尼可抑制细胞增殖并诱导细胞凋亡,有望成为卵巢癌的再治疗药物,为改善患者预后提供了一种新方法。
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Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction.

Background/aim: Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer.

Materials and methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes.

Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction.

Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.

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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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