Orally available tubulin inhibitor VERU-111 enhances antitumor efficacy in paclitaxel-resistant lung cancer.
Orally available tubulin inhibitor VERU-111 enhances antitumor efficacy in paclitaxel-resistant lung cancer.
复制标题
口服微管蛋白抑制剂VERU-111增强紫杉醇耐药肺癌的抗肿瘤疗效。
DOI：
10.1016/j.canlet.2020.09.004
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发表时间：
2020-12-28
期刊：
影响因子：
9.7
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Mahmud F;Deng S;Chen H;Miller DD;Li W
Lung cancer is the most common cause of cancer associated mortality. Chemotherapeutic agents, such as paclitaxel, are important treatment options but drug resistance often develops upon prolonged use. We report here the preclinical evaluation of a new orally available tubulin inhibitor, VERU-111, which can overcome several ABC-transporter mediated multi-drug resistance associated with taxane treatment. In vitro, VERU-111 prevents cell proliferation, invasion, migration and colony formation in both paclitaxel-sensitive and paclitaxel-resistant A549 lung cancer cells. VERU-111 effectively inhibits tubulin polymerization, arrests cells in G2/M phase, and induces cancer cell apoptosis. Further evaluation of various apoptotic proteins revealed that treatment of VERU-111 increases the expression of cleaved-PARP, cleaved-caspase-3 and p-histone H3 proteins. In vivo, orally administered VERU-111 in a paclitaxel-sensitive A549 xenograft model strongly inhibits tumor growth in a dose-dependent manner and is equally potent with paclitaxel. When tested in a highly paclitaxel-resistant A549/TxR tumor model, VERU-111 is as effective as the parental A549 model in significantly reducing the tumor volume, whereas paclitaxel is essentially ineffective. Collectively, this study showed that VERU-111 is a promising new generation of anti-tubulin agent for the treatment of taxane-resistant lung cancer.
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BZML 是一种新型秋水仙碱结合位点抑制剂，通过抑制 P-gp 功能和诱导有丝分裂灾难来克服 A549/Taxol 细胞的多药耐药性
影响因子：
9.7
作者：
Bai, Zhaoshi;Gao, Meiqi;Wu, Yingliang
通讯作者：
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