除莠霉素A对Karpas299和L428细胞增殖与凋亡的比较研究

Proliferation and apoptosis of Karpas299 and L428 cells induced by herbimycin A

目的:探讨酪氨酸激酶抑制剂除莠霉素A(HA)对CD30+间变性大细胞淋巴瘤细胞株Karpas299和霍奇金淋巴瘤细胞株L428细胞增殖和凋亡的影响。方法:采用免疫细胞化学检测Kar-pas299和L428细胞ALK的表达,MTT法检测HA对两株细胞增殖活力的影响,流式细胞仪检测HA处理后两株细胞的细胞周期、凋亡率的变化,HE染色观察细胞凋亡改变。结果:Karpas299细胞表达ALK,L428细胞则不表达;HA对两株细胞的增殖活力均有抑制作用,呈剂量和时间依赖性,P<0.05;HA对Karpas299细胞的作用比L428更为显著,P<0.05;用HA处理24h,G1期细胞和凋亡率均高于对照组,P<0.05;Karpas299细胞高于L428细胞,P<0.05;两株细胞均出现凋亡形态改变。结论:HA明显抑制两株细胞增殖,阻滞细胞周期于G1期,以Karpas299细胞作用更为明显,其机制可能与该细胞表达酪氨酸激酶受体ALK蛋白有关。

OBJECTIVE：To study the effect of tyrosine kinase inhibitor herbimycin A（HA）on cellular proliferation and apoptosis of CD30＋ human anaplastic large-cell lymphoma Karpas299 cells and Hodgkin＇s lymphoma L428 cells.METHODS：The expression of ALK in Karpas299 and L428 cells was determined by immunocytochemical staining.MTT assay was used to evaluate the proliferation of Karpas299 and L428 cells induced by HA.Flow cytometry was used to measure the changes of cell cycle and apoptosis rate of two cell lines,which were treated with HA.The morphological changes of apoptosis were observed by hematoxylin-eosin（HE）staining.RESULTS：ALK was expressed in Karpas299 cells but absent in L428 cells.The cell proliferation of Karpas299 and L428 cells cultured with HA was decreased significantly in a dose-dependent and time-dependent manner（P0.05）.The inhibition of HA on the proliferation of Karpas299 cells was more significant than that of L428 cells（P0.05）.Compared with the control groups,the cells in G1 phase and apoptosis rate of the treatment groups were increased significantly after being cultured with HA for 24 hours,especially for Karpas299 cells（P0.05）.The morphological changes of apoptosis were seen in the two cell lines after exposure to HA.CONCLUSION：HA can inhibit the cell proliferation of two cell lines effectively,and arrest cell cycle in G1 phase,especially for Karpas299 cells,which may be related to the expression of ALK protein.