研究动态
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异丙酚与顺铂或多柔比星在人卵巢癌细胞中的协同机制。

The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.

发表日期:2024 Sep 14
作者: Sung-How Sue, Wei-Cheng Tseng, Zih-Syuan Wu, Shih-Ming Huang, Jia-Lin Chen, Zhi-Fu Wu, Hou-Chuan Lai
来源: Journal of Ovarian Research

摘要:

大多数卵巢癌病例确诊时已属晚期,导致预后不佳,5 年生存率相对较低。虽然早期肿瘤切除可能非常有效,但初次治疗后的复发仍然是死亡的重要原因。异丙酚是癌症切除手术中常用的静脉麻醉剂。先前的研究表明,异丙酚麻醉与接受上皮性卵巢癌择期手术的患者的生存率提高有关。然而,潜在的抗肿瘤机制尚未完全了解。本研究旨在揭示丙泊酚单独使用以及与顺铂或多柔比星联合使用对人 SKOV3 和 OVCAR3 卵巢癌细胞的抗肿瘤特性。我们应用流式细胞术分析线粒体膜电位、细胞凋亡和自噬、集落形成、迁移和蛋白质印迹分析。鉴于化疗是治疗晚期和复发性卵巢癌的主要临床方法,因此必须解决当前化疗的局限性特别是顺铂和阿霉素的使用,往往因其副作用和耐药性的发展而受到限制。首先,异丙酚与顺铂和阿霉素在 SKOV3 细胞中具有协同作用。此外,我们的数据进一步表明,异丙酚抑制 SKOV3 和 OVCAR3 细胞中的集落形成,破坏线粒体膜电位,并诱导细胞凋亡和自噬。最后,异丙酚与顺铂或多柔比星联合对 SKOV3 和 OVCAR3 细胞中线粒体膜电位、细胞凋亡、自噬和上皮间质转化的影响不同,具体取决于 p53 状态。 总之,重新利用异丙酚可以为现有的卵巢癌化疗策略。它有望克服对顺铂或多柔比星的耐药性,并可能减少所需的化疗剂量和相关副作用,从而改善治疗结果。© 2024。作者。
Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood.This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis.Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status.In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.© 2024. The Author(s).