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3-溴阿克拉林通过抑制 MAPK 通路对小细胞肺癌的抗肿瘤作用。

Antitumor effects of 3-bromoascochlorin on small cell lung cancer via inhibiting MAPK pathway.

机构信息

School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangdong Province Engineering Laboratoty for Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

出版信息

Cell Biol Int. 2021 Nov;45(11):2380-2390. doi: 10.1002/cbin.11674. Epub 2021 Aug 1.

Abstract

Small cell lung cancer (SCLC) was defined as a recalcitrant cancer, and novel therapies are urgently needed. Marine natural products (MNPs) may bring continuing hope for treatment of SCLC. In this study, 3-bromoascochlorin (BAS), an MNP isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, was primarily screened out with antiproliferative activity towards SCLC cell lines. Then western blot analysis (WB) and flow cytometry were conducted, and we found BAS could induce the apoptosis of H446 and H69AR cells. Besides, BAS could suppress the invasion and migration of H446. In an SCLC xenograft mice model, BAS inhibited the growth of tumor without affecting the body weight of mice. Finally, the underlying mechanisms were preliminarily explored. According to the results of RNA-seq, reverse transcription-quantitative polymerase chain reaction, and WB, our results revealed that BAS exerted antitumor activity via inhibiting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway. Collectively, these results indicated that BAS can be used as a promising compound for the treatment of human SCLC.

摘要

小细胞肺癌(SCLC)被定义为一种难治性癌症,迫切需要新的治疗方法。海洋天然产物(MNPs)可能为 SCLC 的治疗带来持续的希望。在这项研究中,3-溴藻胆蛋白(BAS),一种从珊瑚来源的真菌 Acremonium sclerotigenum GXIMD 02501 中分离出来的 MNPs,主要通过对 SCLC 细胞系的增殖活性进行筛选。然后进行了 Western blot 分析(WB)和流式细胞术,我们发现 BAS 可以诱导 H446 和 H69AR 细胞凋亡。此外,BAS 可以抑制 H446 的侵袭和迁移。在 SCLC 异种移植小鼠模型中,BAS 抑制肿瘤生长而不影响小鼠体重。最后,初步探讨了潜在机制。根据 RNA-seq、逆转录定量聚合酶链反应和 WB 的结果,我们的结果表明 BAS 通过抑制丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)通路发挥抗肿瘤活性。总之,这些结果表明 BAS 可以用作治疗人类 SCLC 的有前途的化合物。

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