The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line.
The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line.
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DOI：
10.1016/j.apsb.2015.07.008
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Mo SL
中科院分区：
文献类型：
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作者：
Xie J;Liu J;Liu H;Liang S;Lin M;Gu Y;Liu T;Wang D;Ge H;Mo SL
探讨丹参酮IIA对人非小细胞肺癌A549细胞增殖的影响及其对VEGF/VEGFR信号通路的可能机制。丹参酮IIA与其靶蛋白相互作用的探索为研究中药活性成分的抗癌机制提供了可行的平台。采用 CCK-8 法评估丹参酮 IIA (2.5−80 μmol/L) 分别处理 24、48 和 72 h 的 A549 细胞的增殖活性。流式细胞术用于检测细胞凋亡和细胞周期扰动。通过蛋白质印迹研究 VEGF 和 VEGFR2 表达。使用Discovery Studio 2.1中的CDOCKER算法通过分子对接分析评估丹参酮IIA在VEGFR2蛋白晶体结构中的结合模式。 CCK-8结果显示，丹参酮IIA能够显着抑制A549细胞增殖，且呈剂量和时间依赖性。流式细胞术结果显示，试验组细胞凋亡率高于媒介物对照，丹参酮IIA处理的细胞在S期积累，高于媒介物对照。此外，Western blot 中 VEGF 和 VEGFR2 的表达降低。最后，分子对接分析表明，丹参酮IIA以其独特的模式能够稳定地对接至VEGFR2蛋白的激酶结构域，与Cys917形成氢键，与Val848形成π-π堆积相互作用。总之，丹参酮IIA可能抑制A549增殖，诱导细胞凋亡和细胞周期停滞在S期。该药物可能通过靶向 VEGF/VEGFR2 的蛋白激酶结构域来抑制血管生成。探讨丹参酮IIA对人非小细胞肺癌A549细胞增殖的影响及其对VEGF/VEGFR信号通路的可能机制。丹参酮IIA与其靶蛋白相互作用的探索为研究中药活性成分的抗癌机制提供了可行的平台。
The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5−80 μmol/L) for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π–π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2. The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs.