Bioactive tanshinone I inhibits the growth of lung cancer in part via downregulation of Aurora A function.
Bioactive tanshinone I inhibits the growth of lung cancer in part via downregulation of Aurora A function.
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DOI：
10.1002/mc.21888
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发表时间：
2013-07
影响因子：
4.6
通讯作者：
Zhou, Jin-Rong
中科院分区：
文献类型：
--
作者：
Li, Yanli;Gong, Yi;Li, Linglin;Abdolmaleky, Hamid M.;Zhou, Jin-Rong
肺癌是全球癌症死亡的首要原因，寻找新型有效且安全的肺癌预防药物仍然是肺癌研究的重中之重。在本研究中，我们评估了来自中药丹参的生物活性丹参酮——隐丹参酮（CT）、丹参酮I（T1）和丹参酮IIA（T2A）对肺癌细胞系增殖抑制的作用。丹参酮在体外抑制肺癌细胞增殖，其中T1的作用最强，通过细胞周期阻滞和诱导细胞凋亡来实现。基因功能检测表明，通过小干扰RNA敲低极光激酶A（Aurora A）可显著消除T1在体外的活性，这表明极光激酶A是T1的一个重要功能靶点。我们进一步在小鼠模型中评估了T1对H1299非小细胞肺癌细胞生长的效果。丹参酮I以剂量依赖的方式抑制H1299肺癌肿瘤的生长。200mg/kg体重的丹参酮I使最终肿瘤重量显著降低34%（P<0.05），同时肺癌细胞的增殖抑制率和凋亡诱导率分别为54%（P<0.001）和193%（P<0.001），肺癌肿瘤血管生成抑制率为72%（P<0.001），极光激酶A表达降低67%（P<0.001）。另一方面，T1并未显著改变食物摄入量或体重。我们的研究结果提供了实验证据，表明T1可能是一种预防肺癌进展的有效且安全的药物，极光激酶A可能是T1抗肺癌作用的一个重要分子靶点。
Lung cancer is the leading cause of cancer death in the world, and the searching for novel efficacious and safe agents for lung cancer prevention remains the top priority of lung cancer research. In the present study, we evaluated the effect of bioactive tanshinones from a Chinese herb Salvia Miltiorrhiza, Cryptotanshinone (CT), Tanshinone I (T1) and Tanshinone IIA (T2A), on the proliferation inhibition of lung cancer cell lines. Tanshinones inhibited the lung cancer cell proliferation in vitro, with T1 the most potent, via cell cycle arrest and apoptosis induction. Gene function assay showed that Aurora A knockdown by siRNA dramatically eliminated the T1 activity in vitro, suggesting that Aurora A is an important functional target for T1. We further evaluated the effectiveness of T1 on the growth of H1299 non-small lung cancer cell in a mouse model. Tanshinone I inhibited the growth of H1299 lung tumor in a dose-dependent manner. Tanshinone I at 200mg/kg body weight significantly reduced final tumor weight by 34% (P<0.05) associated with inhibiting proliferation and inducing apoptosis of lung cancer cells by 54% (P<0.001) and 193% (P<0.001) respectively, inhibiting lung tumor angiogenesis by 72% (P<0.001), and reducing Aurora A expression by 67% (P<0.001). On the other hand, T1 did not significantly alter food intake or body weight. Our results provided experimental evidence to suggest that T1 may be an efficacious and safe agent for the prevention of lung cancer progression and Aurora A may be an important molecular target for T1 action against lung cancer.
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影响因子：
5.7
作者：
Dar AA;Goff LW;Majid S;Berlin J;El-Rifai W
通讯作者：
El-Rifai W
影响因子：
64.5
作者：
Hirota, T;Kunitoku, N;Saya, H
通讯作者：
Saya, H
影响因子：
4.3
作者：
Lee, W. Y. W.;Chiu, L. C. M.;Yeung, J. H. K.
通讯作者：
Yeung, J. H. K.
影响因子：
4.6
作者：
Mai, Zhiming;Blackburn, George L.;Zhou, Jin-Rong
通讯作者：
Zhou, Jin-Rong
影响因子：
4.8
作者：
Matarasso, Noa;Bar-Shira, Anat;Orr-Urtreger, Avv
通讯作者：
Orr-Urtreger, Avv