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目的:探究伊马替尼衍生物TEB-415和伊马替尼对多发性骨髓瘤细胞U226,H929,RPMI8226,MM1R和MM1S增殖抑制作用。方法:通过改良伊马替尼的化学基团,合成了伊马替尼的衍生物TEB-415。以不同浓度的TEB-415,伊马替尼和硼替佐米处理U226,H929,RPMI8226,MM1R和MM1S细胞72 h,应用CCK-8法检测细胞的增殖水平,观察细胞形态,并计算IC_(50)。结果:TEB-415可显著抑制H929和RPMI8226骨髓瘤细胞的活力。TEB-415浓度<0.1 nmol/L时,>50%H929细胞死亡,而伊马替尼半数抑制浓度(IC_(50))为0.123 mol/L,硼替佐米半数抑制浓度(IC_(50))为0.03 nmol/L。TEB-415浓度11.9 mol/L时,>50%RPMI8226骨髓瘤细胞死亡,而伊马替尼浓度达到12.8mol/L时,细胞仍然状态良好。结论:TEB-415对多发性骨髓瘤细胞H929的杀伤能力远远强于伊马替尼,仅次于硼替佐米。TEB-415对伊马替尼不敏感的RPMI8226细胞,仍然具有一定的杀伤作用。
Objective: To investigate the inhibitory effects of imatinib derivatives TEB-415 and imatinib on the proliferation of multiple myeloma cells U226, H929, RPMI8226, MM1R and MM1S. Methods: Imatinib derivative TEB-415 was synthesized by modifying the chemical group of imatinib. U226, H929, RPMI8226, MM1R and MM1S cells were treated with different concentration of TEB-415, imatinib and bortezomib for 72 h. Cell proliferation was measured by CCK-8 assay. Cell morphology was observed and IC 50 ). Results: TEB-415 significantly inhibited the viability of H929 and RPMI8226 myeloma cells. 50% H929 cells died when the concentration of TEB-415 was less than 0.1 nmol / L, while the half inhibitory concentration (IC 50) of imatinib was 0.123 mol / L and the median inhibitory concentration of bortezomib IC 50, 0.03 nmol / L. When the concentration of TEB-415 was 11.9 mol / L,> 50% of RPMI8226 myeloma cells died, while the imatinib concentration reached 12.8 mol / L, the cells were still in good condition. Conclusion: TEB-415 is more potent than imatinib in killing multiple myeloma cells H929 after bortezomib. TEB-415 is not sensitive to imatinib RPMI8226 cells, still have some killing effect.