Artesunate belongs to a class of medications derived from the sweet wormwood plant (Artemisia annua) known as artemisinins. Artesunate has traditionally been used as a frontline treatment for severe malaria but has also demonstrated antineoplastic activity against various malignancies, including ovarian cancer. Data suggest that artesunate exacerbates cellular oxidative stress, triggering apoptosis. In the current study, we investigated the ability of navitoclax, an inhibitor of the antiapoptotic Bcl-2 protein family, to enhance artesunate efficacy in ovarian cancer cells. Artesunate and navitoclax both demonstrated antiproliferative effects on 2D and 3D ovarian cancer cell models as single agents. Upon combination of navitoclax with artesunate, antineoplastic drug synergy was also observed in each of the 2D cell lines and ovarian tumor organoid models tested. Further investigation of this drug combination using intraperitoneal CAOV3 xenograft models in BALB/scid mice showed that the artesunate/navitoclax doublet was superior to single-agent artesunate and vehicle control treatment. However, it did not outperform single-agent navitoclax. With optimization, this drug combination could provide a new therapeutic option for ovarian cancer and warrants further preclinical investigation.
青蒿琥酯属于一类从青蒿植物中提取的药物，统称为青蒿素衍生物。传统上，青蒿琥酯被用作重症疟疾的一线治疗药物，但研究也表明其对多种恶性肿瘤（包括卵巢癌）具有抗肿瘤活性。数据显示，青蒿琥酯会加剧细胞氧化应激，从而触发细胞凋亡。在本研究中，我们探讨了navitoclax（一种抗凋亡Bcl-2蛋白家族抑制剂）增强青蒿琥酯对卵巢癌细胞疗效的能力。青蒿琥酯和navitoclax作为单一药物在二维和三维卵巢癌细胞模型中均显示出抗增殖作用。将navitoclax与青蒿琥酯联合使用时，在所有测试的二维细胞系和卵巢肿瘤类器官模型中也观察到了抗肿瘤药物的协同作用。通过使用BALB/scid小鼠腹腔CAOV3异种移植模型对该药物组合进行进一步研究，结果显示青蒿琥酯/navitoclax联合用药优于单药青蒿琥酯和载体对照治疗，但未超越单药navitoclax的疗效。通过优化，该药物组合可能为卵巢癌提供新的治疗选择，值得进一步的临床前研究。
肿瘤(癌症)患者之家