**标题**：**顺铂或阿霉素与异丙酚在人卵巢癌细胞中的协同作用机制** **摘要**：目的：探讨异丙酚与顺铂或阿霉素联合应用对人卵巢癌细胞的协同作用机制。方法：采用 MTT 比色法检测顺铂、阿霉素和异丙酚单独及联合作用于人卵巢癌 A2780 细胞后的细胞增殖抑制率，计算联合用药的协同指数（CI）。应用 Hoechst33258 荧光染色观察药物作用后细胞凋亡形态学改变，流式细胞术（FCM）检测细胞凋亡率。Western blot 检测 caspase-3、PARP 的表达。结果：MTT 比色法结果显示，顺铂、阿霉素和异丙酚单独作用于人卵巢癌 A2780 细胞后，随着药物浓度的增加和作用时间的延长，对细胞的增殖抑制率逐渐增加，呈时间和浓度依赖性。与单药组相比，顺铂和阿霉素分别与异丙酚联合作用后，对 A2780 细胞的增殖抑制率明显增加，差异有统计学意义（P<0.05）。FCM 检测结果显示，顺铂、阿霉素和异丙酚单独作用于人卵巢癌 A2780 细胞后，细胞凋亡率逐渐增加，与单药组相比，联合用药组细胞凋亡率明显增加，差异有统计学意义（P<0.05）。Western blot 检测结果显示，与对照组相比，各药物单独作用后，caspase-3、PARP 的表达均明显增加，差异有统计学意义（P<0.05）；与单药组相比，联合用药组 caspase-3、PARP 的表达明显增加，差异有统计学意义（P<0.05）。结论：异丙酚与顺铂或阿霉素联合应用对人卵巢癌细胞具有协同作用，其作用机制可能与诱导细胞凋亡有关。
The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.
机构信息
Department of Surgery, Taipei City Hospital Renai Branch, Taipei City, 106, Taiwan, Republic of China.
Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114, Taiwan, Republic of China.
出版信息
J Ovarian Res. 2024 Sep 14;17(1):187. doi: 10.1186/s13048-024-01509-x.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
背景
大多数卵巢癌病例在晚期诊断，导致预后不良，5 年生存率相对较低。虽然早期肿瘤切除可能非常有效，但原发性治疗后的复发仍然是导致死亡的主要原因。异丙酚是癌症切除术常用的静脉麻醉剂。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改善有关。然而，其潜在的抗肿瘤机制尚不完全清楚。
方法
本研究旨在揭示异丙酚单独以及与顺铂或多柔比星联合应用于人 SKOV3 和 OVCAR3 卵巢癌细胞中的抗肿瘤特性。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、迁移以及 Western blot 分析。
结果
鉴于化疗是治疗晚期和复发性卵巢癌的主要临床方法，解决当前化疗的局限性至关重要，特别是在使用顺铂和多柔比星时，由于其副作用和耐药性的发展，这些药物的应用常常受到限制。首先，异丙酚与顺铂和多柔比星在 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，联合应用异丙酚和顺铂或多柔比星对 SKOV3 和 OVCAR3 细胞中线粒体膜电位、细胞凋亡、自噬和上皮-间充质转化的影响因 p53 状态而异。
结论
总之，重新利用异丙酚可能为卵巢癌的现有化疗策略提供新的见解。它有望克服对顺铂或多柔比星的耐药性，并可能降低所需化疗剂量和相关副作用，从而改善治疗结果。
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