摘要
目的评价酪氨酸激酶受体抑制剂AL3810对人肺腺癌细胞A549的体外及体内抗肿瘤作用。方法①采用MTT法评价AL3810对13种人体肿瘤细胞株和人胚肺细胞的体外增殖抑制作用。②采用流式细胞仪检测AL3810诱导细胞凋亡的能力及其对细胞周期的影响。③采用流式细胞仪检测AL3810诱导Caspase-3活化的作用。④划痕试验评价AL3810对A549细胞体外迁移的影响。⑤以人肺腺癌A549裸鼠异种移植瘤模型评价AL3810对肿瘤生长抑制作用的量效关系。结果AL3810对大部分细胞均有很强的生长抑制作用。其能诱导A549细胞凋亡且具有时效性,能将细胞周期阻滞于G0-G1期;能将无活性的Caspase-3前体活化且具有时效关系;能时间依赖性地显著抑制A549细胞的体外迁移;对A549异种移植瘤生长具有良好的抑制作用,且具有量效关系。结论酪氨酸激酶受体抑制剂AL3810具有显著的抗肿瘤活性,能剂量依赖性地抑制A549的生长。可能机制为诱导肿瘤细胞凋亡和阻滞细胞周期于G0-G1期、诱导细胞内Caspase-3活化、抑制细胞迁移等,值得进一步开发。
Objective To test the anti-tumor effect of AL3810 on A549 human lung adenocarcinoma.Methods ①The antiproliferative effects of AL3810 against 13 human carcinoma cell lines and MRC-5 cell line in vitro were observed by MTT assay.②The effects of AL3810 on cell cycle distribution and induction of apoptosis were assessed by flow cytometry analysis.③The effects of AL3810 on the active caspase-3 of A549 cell line were assessed by flow cytometry analysis.④The effect of AL3810 on cell migration was determined by wound assay.⑤The dose-effect relationship on antitumor effect of AL3810 was evaluated in vivo with the model of nude mice bearing A549 xenografts.Results AL3810 inhibited most of the cell lines significantly.AL3810 had the ability to induce apoptosis of A549 cell,and also showed in time dependent manner.In addition,AL3810 was also observed to block cells in G0-G1phase of cell cycle.AL3810 activated the caspase-3 in cells with a time dependent manner.Cell migration was also inhibited by AL3810 and the effects were time dependent.AL3810 showed significant inhibitive effects and the dose-effect relationship of tumor growth in xenografted nude mice.Conclusion AL3810 inhibited the proliferation of several tumor cell lines while differed in inhibition degree.The mechanisms of AL3810 might be associated with induction of tumor cells apoptosis,G0-G1 phase arrest,activation of caspase-3 and inhibiting the migration of A549 cell.
出处
《世界临床药物》
CAS
2013年第4期206-211,共6页
World Clinical Drug
