目的 探討苦參堿對肺癌A549細(xì)胞增殖、侵襲和血管生成抑制作用以及其作用機(jī)制。方法 不同濃度苦參堿組加入到A549人肺癌細(xì)胞株中，利用ELISA法研究了苦參堿對EGFR-TPK的抑制作用，利用MTT法測定苦參堿對A549細(xì)胞的抑制作用，Transwell法檢測苦參堿對肺癌A549細(xì)胞侵襲的抑制作用，酶標(biāo)儀法檢測苦參堿對細(xì)胞凋亡蛋白caspase 3活性的影響，Western blotting法檢測苦參堿存在下A549中VEGF、HIF-1α的表達(dá)。結(jié)果 苦參堿對EGFR-TPK半數(shù)抑制率為11.26±1.02 μmol/L，對肺癌A549細(xì)胞生長IC₅₀為30.45±3.02 μmol/L，都具有良好的抑制能力，但對于MRC-5細(xì)胞表現(xiàn)了較低的毒性；苦參堿與對照組相比能夠誘導(dǎo)腫瘤細(xì)胞穿過人工基底膜的數(shù)量減少，差異有顯著性（P<0.05）；與對照組比較，苦參堿能顯著提高A549中凋亡蛋白caspase 3活性（P<0.05）；苦參堿能夠下調(diào)HIF-1α和VEGF的表達(dá)。結(jié)論 苦參堿可降低EGFR-TPK活性和HIF-1α、VEGF的表達(dá)，激活caspase 3活性，對肺癌腫瘤A549細(xì)細(xì)胞的侵襲、增殖和血管生成產(chǎn)生抑制作用。

Objective To study the inhibition of matrine on proliferation, invasion, and angiogenesis of A549 lung cancer tumor cells, and explore its mechanisms. Methods Matrine with various concentration was added to human lung cancer A549 cell line. The inhibitory effect of matrine against EGFR-TPK was investigated by ELISA method, the inhibitory rate of matrine against A549 was determined by MTT method, and inhibitory effect of matrine on invasion of lung cancer A549 cells was studied by Transwell assay. The effect of matrine on the activity of apoptotic protein caspase 3 was detected by enzyme labeling method, and finally the effect of matrine on expression of angiogenesis related protein VEGF and HIF-1α of A549 tumor cells were discussed. Results Matrine has good restrain ability on EGFR-TPK and A549 cells with IC₅₀ of (11.26±1.02) and (30.45±3.02) μmol/L, but showed low toxicity for MRC-5 cells. Compared with the control group, matrine could induce the number of tumor cells to pass through the artificial basement membrane, with significant difference between two groups (P < 0.05). Compared with the control group, matrine could significantly increase caspase 3 activity of A549 (P < 0.05), and the expression of angiogenesis related protein VEGF and HIF-1α of A549 tumor cells were down-regulated. Conclusion Matrine can reduce the activity of EGFR-TPK and the expression of HIF-1 and VEGF, activate the activity of caspase 3, and inhibit the invasion, proliferation and angiogenesis of lung cancer A549 cells.

河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃項(xiàng)目（201203068）