Cryptotanshinone inhibits cellular proliferation of human lung cancer cells through downregulation of IGF-1R/PI3K/Akt signaling pathway
Cryptotanshinone inhibits cellular proliferation of human lung cancer cells through downregulation of IGF-1R/PI3K/Akt signaling pathway
复制标题
隐丹参酮通过下调 IGF-1R/PI3K/Akt 信号通路抑制人肺癌细胞的细胞增殖。
DOI：
10.3892/or.2018.6638
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发表时间：
2018-11-01
期刊：
影响因子：
4.2
通讯作者：
Yu, Bentong
中科院分区：
文献类型：
--
作者：
Zhang, Jingtao;Wen, Guilan;Yu, Bentong
肺癌是世界范围内最常见的恶性肿瘤之一。隐丹参酮（Cryptotanshinone，CPT）是一种从天然植物中提取的二萜醌类化合物，对多种癌症包括肺癌具有抗癌作用。然而，CPT阻止肺癌细胞生长的机制在很大程度上是未知的。本研究采用MTT法、克隆形成实验、伤口愈合实验和Western blotting实验，探讨CPT对人肺癌细胞增殖和迁移的影响及其可能的细胞信号转导机制。结果表明，CPT对A549和H1299细胞具有抗增殖作用。同时，A549细胞的迁移也被CPT处理显著抑制。进一步研究表明，CPT不仅能抑制胰岛素样生长因子1受体（IGF-1 R）和RAC-α丝氨酸/苏氨酸蛋白激酶（Akt）的基础磷酸化水平，而且能阻断IGF-1诱导的IGF-1 R和Akt磷酸化。最后，证明CPT预处理抑制IGF-1诱导的A549和H1299细胞的细胞增殖。总之，本研究的结果表明，CPT通过抑制IGF-1 R介导的磷酸肌醇3-激酶/Akt信号通路抑制肺癌细胞的增殖和迁移。这些数据提供了证据，CPT可以被开发为用于治疗肺癌的潜在治疗剂。
Lung cancer is one of the most commonly diagnosed malignancies worldwide. Cryptotanshinone (CPT) is a diterpene quinone compound extracted from natural plants and has been reported to have anticancer effects in several cancers including human lung cancer. However, the mechanism by which CPT acts to prevent lung cancer cell growth is largely unknown. In the present study, by using MTT assay, colony formation assay, wound healing and western blotting assays, the effects of CPT on the cell proliferation and migration of human lung cancer cells and the potential cellular signaling mechanisms were investigated. The data demonstrated that CPT exhibited anti-proliferative effects against A549 and H1299 cells. In parallel, the migration of A549 cells was also markedly inhibited by CPT treatment. Further study indicated that CPT not only inhibited the basal phosphorylation level of insulin-like growth factor 1 receptor (IGF-1R) and RAC-alpha serine/threonine-protein kinase (Akt), but also blocked IGF-1 induced IGF-1R and Akt phosphorylation. Finally, it was demonstrated that pretreatment with CPT inhibited IGF-1 induced cell proliferation of A549 and H1299 cells. In conclusion, the results of the present study indicated that CPT inhibits the proliferation and migration of lung cancer cells via a mechanism that involves inhibiting the IGF-1R-mediated phosphoinositide 3-kinase/Akt signaling pathway. The data provides evidence that CPT could be developed as a potential therapeutic agent for the treatment of lung cancer.