Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan 475001, China.
Eur J Pharmacol. 2010 Mar 25;630(1-3):121-30. doi: 10.1016/j.ejphar.2009.12.014. Epub 2009 Dec 28.
The dose-related toxicity of anticancer drugs in chemotherapy of clinical carcinoma is the major obstacle to prolonged survival, we want to investigate selective therapeutic efficacy of baicalin on lung carcinoma and explain the basis underlying this phenomenon. In vitro, baicalin inhibited cell proliferation of human lung carcinoma A549 and mouse lewis lung cancer (LLC) in a dose- and time-dependent manner. The inhibitory activity of baicalin against cancer cells was promoted by superoxide dismutase (SOD) addition or hypoxia-inducible factor-1alpha (HIF-1alpha) knockdown and was reduced by SOD knockdown but not hypoxia. In vivo, baicalin suppressed tumor growth and prolonged survival in C57BL/6 mice bearing LLC tumor and nude mice bearing A549 carcinoma without systemic toxicity. Further studies showed that baicalin inhibited HIF-1alpha and enhanced SOD activity without affecting catalase and glutathione-S-transferase (GST) in cancer cells. In addition, baicalin also exhibited a superoxide anion scavenging activity. In conclusion, baicalin could selectively suppress lung carcinoma and lung metastasis by SOD mimic and HIF-1alpha inhibition.
抗癌药物在临床癌症化疗中的剂量相关性毒性是延长生存时间的主要障碍，我们希望研究黄芩苷对肺癌的选择性治疗效果，并解释这种现象的基础。在体外，黄芩苷以剂量和时间依赖的方式抑制人肺癌 A549 和小鼠 Lewis 肺癌 (LLC) 的细胞增殖。黄芩苷对癌细胞的抑制活性通过添加超氧化物歧化酶 (SOD) 或缺氧诱导因子-1alpha (HIF-1alpha) 敲低而增强，并通过 SOD 敲低而不是缺氧而降低。在体内，黄芩苷抑制 C57BL/6 小鼠携带 LLC 肿瘤和裸鼠携带 A549 癌的肿瘤生长并延长生存时间，而没有全身毒性。进一步的研究表明，黄芩苷抑制 HIF-1alpha 并增强 SOD 活性，而不影响癌细胞中的过氧化氢酶和谷胱甘肽-S-转移酶 (GST)。此外，黄芩苷还具有清除超氧阴离子的活性。总之，黄芩苷可以通过模拟 SOD 和抑制 HIF-1alpha 选择性抑制肺癌和肺转移。
