Objective The derivative of Gefitinib was used to treat glioma cells in vitro to explore a more effective new drug for the clinical treatment of astrocytoma. Methods (1) Fifteen kinds of gefitinib derivatives, gefitinib and temozolomide were used to treat glioma cells, and the effect of 0, 10, 15, 20, 25 and 30 μmol/L of each kind of drug on cell proliferation was detected by by MTT assay , respectively. (2) To calculate the concentration of IC50 , then select lower IC50 of derivativs combinate gefitinib and temozolomide with 10, 20 and 30 μmol/L to treat cells, then the apoptosis of cells were detected by flow cytometry. Expression of p-EGFR was detected by western–blot assay. Results (1) NO.LPY-5,9,11, but not other derivatives of Gefitinib could effectively inhibit the growth of cells. (2) IC50 of NO.LPY-9 was less than that of the 5th drug, and both of them were lower than those of gefitinib and temozolomide; NO. LPY-11 was excluded. (3) The cell apoptosis of No. LPY-9 was higher than that of gefitinib and temozolomide , respectively. However, No.LPY-9-induced cell apoptosis was significantly higher than that of No. LPY-5-induced cell. (4) Levels of p-EGFR expression in No.LPY-9 and gefitini-induced cells were significantly lower than that in the negative control group. Conclusion No.LPY-9 has asignificant inhibitory effect on glioma cells in vitro , resulting from the inhibition of the ERFR-mediated signaling pathways and induction of cell apoptosis.%目的:采用吉非替尼衍生物体外干预胶质瘤细胞,为临床治疗探索一种新的药物.方法:(1)以15种吉非替尼衍生物(LPY-号)、 吉非替尼及替莫唑胺干预原代胶质瘤细胞,每种以0、10、15、20、25、30μmol/L 6种浓度干预后行MTT测药物抑制率,筛选作用明显的衍生物;(2)计算药物IC50,选择IC50较低的衍生物与吉非替尼、替莫唑胺以10、20、30μmol/L干预细胞,采用流式细胞术检测细胞凋亡;选择凋亡明显的衍生物和吉非替尼处理细胞,用western-blot检测磷酸化的表皮生长因子受体(p-EGFR)含量的表达.结果:(1)MTT:LPY-5、9、11号能有效地抑制细胞的生长,其他衍生物筛除.(2)IC50:LPY-9号的IC50低于5号,两者均低于吉非替尼及替莫唑胺;LPY-11号筛除.(2)流式细胞术:LPY-5、9号的细胞凋亡率均高于吉非替尼和替莫唑胺,9号明显高于5号.(4)western-blot:LPY-9号和吉非替尼干预肿瘤细胞后p-EGFR的表达量均低于阴性对照组,且9号更明显;所有结果的差异都具有统计学意义.结论:LPY-9号在体外对胶质瘤细胞有明显抑制作用,其可能是通过抑制ERFR介导的信号传导通路和诱导细胞凋亡来实现的.
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