Novel therapeutic strategy for melanoma based on albendazole and the CDK4/6 inhibitor palbociclib.
Novel therapeutic strategy for melanoma based on albendazole and the CDK4/6 inhibitor palbociclib.
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基于阿苯达唑和 CDK4/6 抑制剂 palbociclib 的黑色素瘤新治疗策略
DOI：
10.1038/s41598-022-09592-0
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发表时间：
2022-04-05
影响因子：
4.6
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Zhu L;Yang Q;Hu R;Li Y;Peng Y;Liu H;Ye M;Zhang B;Zhang P;Liu-Smith F;Li H;Liu J
尽管越来越多的患者受益于免疫治疗和靶向治疗，但黑色素瘤仍然无法治愈，发病率不断增加。药物重新定位和再利用是发现和开发新型抗癌药物或联合治疗方案的替代策略。在这项研究中，我们证明，阿苯达唑（ABZ），食品和药物管理局（FDA）批准的广谱抗寄生虫剂，显着抑制黑色素瘤细胞在体外和体内的增殖。RNA测序和流式细胞术分析显示，ABZ将黑色素瘤细胞阻滞在细胞周期的G2/M期，并诱导细胞凋亡。更重要的是，CDK 4/6抑制剂palbociclib作为迄今为止第一个也是唯一一个获批用于癌症治疗的高度特异性CDK抑制剂，在黑色素瘤细胞和小鼠模型中与ABZ治疗显示出显著的协同效应。综上所述，我们揭示了ABZ通过诱导细胞周期阻滞和细胞凋亡在抗黑素瘤增殖中的一种以前未被认识到的功能，并提供了一种新的ABZ加CDK 4/6抑制剂治疗黑素瘤的联合治疗方案。
Although an increasing number of patients benefit from immunotherapy and targeted therapies, melanoma remains incurable with increasing incidence. Drug repositioning and repurposing is an alternative strategy to discover and develop novel anticancer drugs or combined therapeutic regimens. In this study, we demonstrated that albendazole (ABZ), an Food and Drug Administration (FDA)-approved broad-spectrum antiparasitic agent, significantly inhibits the proliferation of melanoma cells in vitro and in vivo. RNA sequencing and flow cytometry analysis revealed that ABZ arrests melanoma cells at the G2/M phase of the cell cycle and induces cell apoptosis. More importantly, the CDK4/6 inhibitor palbociclib, as a member of the first and only class of highly specific CDK inhibitors approved for cancer treatment to date, showed significant synergistic effects with ABZ treatment in melanoma cells and mouse models. Taken together, we revealed a previously unappreciated function of ABZ in antimelanoma proliferation by inducing cell cycle arrest and apoptosis and provided a novel combined therapeutic regimen of ABZ plus CDK4/6 inhibitor treatment in melanoma.
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