BSV163/DOPE介导的TRAIL基因转染与化疗协同作用对抗顺铂耐药性卵巢癌。
BSV163/DOPE-mediated TRAIL gene transfection acts synergistically with chemotherapy against cisplatin-resistant ovarian cancer.
发表日期:2023 Sep 20
作者:
Quoc Manh Nguyen, Pierre-François Dupré, Mathieu Berchel, Rosy Ghanem, Paul-Alain Jaffrès, Frédérique d'Arbonneau, Tristan Montier
来源:
Cell Death & Disease
摘要:
卵巢癌是全球女性中第七种最常见的被诊断为癌症的肿瘤。大多数患者经历复发并最终死于耐药性疾病,突显了对替代治疗选择的需求。在本文中,我们研究了TRAIL基因通过创新的仿生脂质载体BSV163/DOPE转染在顺铂存在或不存在的情况下,对抗敏感和耐药性的卵巢癌的效果。我们表明BSV163/DOPE能够安全有效地转染卵巢癌细胞系(Caov3,OVCAR3以及我们新开发的顺铂耐药性细胞系CR-Caov3)。此外,TRAIL基因转染与顺铂联合抑制细胞生长效果更加显著(Caov3细胞经过联合治疗后减少近50%生长,而单独治疗时分别减少15%或25%),这是由于凋亡率增加、半胱氨酸蛋白酶活性增强和TRAIL死亡受体表达上升所致。最重要的是,这种协同效应也在CR-Caov3细胞中观察到,经过联合治疗后的凋亡率为35%,而TRAIL基因转染后为17%,顺铂处理后为6%。这些结果表明该组合可能具有对敏感和难治性卵巢癌患者的潜在应用。© 2023 The Authors. Chemical Biology & Drug Design published by John Wiley & Sons Ltd.
Ovarian cancer is the seventh most frequently diagnosed cancer among women worldwide. Most patients experience recurrence and succumb eventually to resistant disease, underscoring the need for an alternative treatment option. In the presented manuscript, we investigated the effect of the TRAIL-gene, transfected by an innovative bioinspired lipid vector BSV163/DOPE in the presence or absence of cisplatin, to fight against sensitive and resistant ovarian cancer. We showed that BSV163/DOPE can transfect ovarian cancer cell lines (Caov3, OVCAR3, and our new cisplatin-resistant, CR-Caov3) safely and efficiently. In addition, TRAIL-gene transfection in association with cisplatin inhibited cellular growth more efficiently (nearly 50% in Caov3 cells after the combined treatment, and 15% or 25% by each treatment alone, respectively) owing to an increase in apoptosis rate, caspases activity and TRAIL's death receptors expression. Most importantly, such synergistic effect was also observed in CR-Caov3 cells demonstrated by an apoptosis rate of 35% following the combined treatment in comparison with 17% after TRAIL-gene transfection or 6% after cisplatin exposition. These results suggest this combination may have potential application for sensitive as well as refractory ovarian cancer patients.© 2023 The Authors. Chemical Biology & Drug Design published by John Wiley & Sons Ltd.