Lentivirus-Based Virus-Like Particles Mediate Delivery of Caspase 8 into Breast Cancer Cells and Inhibit Tumor Growth
Lentivirus-Based Virus-Like Particles Mediate Delivery of Caspase 8 into Breast Cancer Cells and Inhibit Tumor Growth
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DOI：
10.1089/cbr.2018.2566
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发表时间：
2019-02-01
影响因子：
3.4
通讯作者：
Yao, Xiaojian
中科院分区：
文献类型：
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作者：
Ao, Zhujun;Chen, Wei;Yao, Xiaojian
目的：细胞凋亡在肿瘤的发生和治疗中发挥着重要作用。能够恢复凋亡信号通路的药物或治疗策略有可能消除癌症。半胱氨酸天冬氨酸氨基转移酶8(CASP8)在导致细胞凋亡的酶促反应中起着至关重要的作用。方法和结果：在这项研究中，作者研究了HIV Gag病毒样颗粒(VLP)与活性CASP8(Gag-CASP8-VLP)结合对乳腺癌生长的抑制作用。他们的数据表明，由口炎病毒G蛋白(VSV-G)假型的Gag-CASP8-VLP可以有效地进入并将活性CASP8送入乳腺癌细胞，导致大量细胞凋亡和死亡。有趣的是，在4T1小鼠乳腺癌模型的肿瘤组织中注射Gag-CASP8-VLPs可以有效地抑制肿瘤的生长，并且越早给药，肿瘤的生长被抑制得越深。结论：GAG-CASP8-VLPs可将CASP8导入乳腺癌细胞，诱导细胞凋亡，抑制肿瘤生长。
Objective: Apoptosis plays an important role in both carcinogenesis and cancer treatment. Drugs or treatment strategies that can restore the apoptotic signaling pathways have the potential to eliminate cancer. Caspase 8 (CASP8) plays a vital role in the propagation of an enzymatic cascade that results in cell apoptosis. Methods and Results: In this study, the authors investigated the inhibitory effects of a HIV Gag virus-like particles (VLPs) that are incorporated with an active CASP8 (Gag-CASP8-VLPs) on the growth of breast cancer. Their data have shown that Gag-CASP8-VLPs, pseudotyped by the stomatitis virus G protein (VSV-G), can efficiently enter and deliver active CASP8 into breast cancer cells, leading to massive cell apoptosis and death. Interestingly, an injection of Gag-CASP8-VLPs in the tumor tissues of a 4T1 mouse breast cancer model can effectively inhibit tumor growth, and the earlier the Gag-CASP8-VLPs is administered, the more profoundly the tumor growth is inhibited. Conclusions: Overall, Gag-CASP8-VLPs can deliver CASP8 into breast cancer cells, induce cell apoptosis, and inhibit tumor growth.