Respiratory and critical care medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Department of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, China.
Chem Biol Drug Des. 2021 Apr;97(4):809-820. doi: 10.1111/cbdd.13810. Epub 2020 Dec 5.
Cisplatin has strong broad-spectrum anticancer activity and is one of the most effective anticancer drugs currently used. The clinical application of cisplatin has led to the resistance of cancer cells to cisplatin. Tachyplesin is an active, natural marine peptide with antitumour activity. In the present study, we investigated whether tachyplesin can be used in non-small cell lung cancer (NSCLC) A549 and H460 cells as well as the cisplatin-resistant human A549/DDP NSCLC cell line. The results revealed that tachyplesin treatment significantly inhibited proliferation and induced apoptosis in A549 and H460 cells and the combination of tachyplesin and cisplatin significantly suppressed migration and improved sensitivity to cisplatin in A549/DDP cells. Further mechanistic examination revealed that tachyplesin induced apoptosis in A549/DDP cells by increasing Fas, FasL and p-RIPK1 levels. These results indicated that tachyplesin induces lung cancer death by activating the Fas, mitochondrial and necroptosis pathways. Tachyplesin could be developed as a candidate drug for cisplatin-resistant NSCLC.
顺铂具有广谱抗癌活性，是目前最有效的抗癌药物之一。顺铂的临床应用导致了癌细胞对顺铂的耐药性。海鞘素是一种具有抗肿瘤活性的天然海洋肽。在本研究中，我们研究了海鞘素是否可以用于非小细胞肺癌（NSCLC）A549 和 H460 细胞以及顺铂耐药的人 A549/DDP NSCLC 细胞系。结果表明，海鞘素处理显著抑制了 A549 和 H460 细胞的增殖并诱导其凋亡，并且海鞘素与顺铂联合应用显著抑制了 A549/DDP 细胞的迁移并提高了其对顺铂的敏感性。进一步的机制研究表明，海鞘素通过增加 Fas、FasL 和 p-RIPK1 水平诱导 A549/DDP 细胞凋亡。这些结果表明，海鞘素通过激活 Fas、线粒体和坏死性凋亡途径诱导肺癌细胞死亡。海鞘素可能被开发为治疗顺铂耐药性 NSCLC 的候选药物。
