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纳米脂质体玉米醇溶蛋白水解物提高肺癌治疗中的细胞凋亡活性和治疗指数。

Nano-liposomal zein hydrolysate for improved apoptotic activity and therapeutic index in lung cancer treatment.

机构信息

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Food Science and Engineering, Faculty of Agriculture, University of Kurdistan, Sanandaj, Iran.

出版信息

Drug Deliv. 2022 Dec;29(1):1049-1059. doi: 10.1080/10717544.2022.2057618.

Abstract

Lung cancer is one of the most common cancers in the world with a high mortality rate. Zein is a protein compound whose protein isolate is not useful and whose protein hydrolysis produces biological activity. By encapsulating this bioactive compound inside the nanoparticles (NPs), it causes itself to reach the tumor site and destroy it rapidly. In this study, the effects of zein hydrolysate (ZH) and nano-liposomal ZH (N-ZH) were investigated on the human A549 cell line. Western blotting and cell cycle analyses showed that ZH and N-ZH caused cytotoxicity. They induced apoptosis via cell cycle arrest at the G0 phase, as well as significant increases in pro-apoptotic genes, such as Bax, caspase-3, -8, -9, and p53, accompanied with significant decreases in the anti-apoptotic marker Bcl-2. Based on the results, the cytotoxic and anticancer effects of N-ZH were higher than those of free ZH. In conclusion, liposomes improved the performance of ZH and dramatically reduced the IC value of ZH. These findings provided the experimental evidence that N-ZH with favorable anticancer activity can be used as a therapeutic agent and strategy for lung cancer treatment in future clinical trials.

摘要

肺癌是世界上最常见的癌症之一,死亡率很高。玉米醇溶蛋白是一种蛋白质化合物,其蛋白质分离物没有用处,而蛋白质水解会产生生物活性。通过将这种生物活性化合物封装在纳米颗粒(NPs)内部,它可以使其自身到达肿瘤部位并迅速破坏肿瘤。在这项研究中,研究了玉米醇溶蛋白水解物(ZH)和纳米脂质体玉米醇溶蛋白(N-ZH)对人 A549 细胞系的影响。Western blot 和细胞周期分析表明,ZH 和 N-ZH 引起细胞毒性。它们通过细胞周期阻滞在 G0 期诱导细胞凋亡,同时显著增加促凋亡基因,如 Bax、caspase-3、-8、-9 和 p53,同时抗凋亡标志物 Bcl-2 显著减少。基于这些结果,N-ZH 的细胞毒性和抗癌作用强于游离 ZH。总之,脂质体提高了 ZH 的性能,显著降低了 ZH 的 IC 值。这些发现为具有良好抗癌活性的 N-ZH 可作为未来临床试验中肺癌治疗的治疗剂和策略提供了实验证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/054f/8979517/bfc2b29ceb64/IDRD_A_2057618_F0001_C.jpg

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