生存素
卡铂
甘薯糖苷
梅尔法兰
拓扑替康
细胞毒性
癌症研究
药理学
医学
视网膜母细胞瘤
化疗
紫杉醇
癌症
依托泊苷
化学
顺铂
体外
内科学
生物化学
基因
作者
Victor Passos Gibson,Rabeb Mouna Derbali,Huu Trong Phan,Houda Tahiri,Christine Allen,Pierre Hardy,Jeanne Leblond Chain
标识
DOI:10.1016/j.ijpharm.2020.119824
摘要
Survivin stands out as one of the most specific cancer targets discovered to date. Although single inhibition, e.g. through small interfering RNA (siRNA), has shown modest results in clinical trials, its combination with drugs holds promise to sensitize cancer cells to chemotherapeutics. In this study, we propose a sequential treatment of siRNA survivin followed by chemotherapy. Firstly, we demonstrated that siRNA-loaded switchable lipid nanoparticles (siLNP) silence survivin in a panel of cancer cell lines. Subsequently, we selected retinoblastoma (RB) as our model to screen four chemotherapeutic agents: carboplatin, topotecan, melphalan or teniposide. The effect of drugs on survivin expression and caspase-3 was investigated by RT-qPCR. The best drug combination was selected measuring the viability, survivin expression and the selectivity of the treatment. Our stepwise method revealed that siRNA delivery by switchable LNP sensitized Y79, but not the healthy APRE-19 cell line, to carboplatin and melphalan cytotoxicity. This ability was validated on primary human RB cells. Finally, the distinct behavior of the drugs demonstrated that a diligent screening of drugs should be envisioned when looking for synergy with survivin. Our sequential approach highlighted carboplatin and melphalan as agents to be investigated in future survivin-associated in vivo testing to tackle RB.
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