吉非替尼和拉帕替尼对HEL细胞增殖的抑制作用

Inhibitory Effect of Gefitinib and Lapatinib on Proliferation of HEL Cells

本研究探讨两种分子靶向治疗药物酪氨酸激酶抑制剂吉非替尼和拉帕替尼对JAK2 V617F阳性的骨髓增殖性疾病(MPD)的潜在治疗作用。吉非替尼(0.5、1、5、10、25μmol/L)和拉帕替尼(0.5、1、2、4、8、16μmol/L)分别作用于携带JAK2 V617F突变的人红白血病细胞株(HEL细胞系)。用MTT法检测2种药物对HEL细胞增殖的影响,流式细胞术检测其对细胞凋亡和细胞周期的影响。结果表明,吉非替尼可明显抑制HEL细胞的增殖,呈浓度依赖性(24和48 h的相关系数为0.991和0.895),48 h的IC50为5.4μmol/L。拉帕替尼作用48 h抑制细胞增殖的IC50为19.6μmol/L。吉非替尼对HEL细胞有显著的诱导凋亡作用,呈浓度依赖性(相关系数为0.896),随药物浓度的增加,凋亡细胞比例的增加。此外,吉非替尼明显地影响细胞周期,将细胞周期阻滞于G0/G1期。结论:吉非替尼和拉帕替尼对HEL细胞有显著的抑制增殖作用,可进一步用于JAK2 V617F阳性的MPD靶向治疗的研究。

This study was aimed to investigate the therapeutic effect of two molecular targeted therapeutic drugs,tyrosine kinase inhibitors gefitinib and lapatinib,on JAK2 V617F positive myeloproliferative disorders（MPD）.The human leukemia cell line（HEL cell line） carrying JAK2 V617F mutation was treated with gefitinib（0.5,1,5,10,25 μmol/L） and lapatinib（0.5,1,2,4,8,16 μmol/L） respectively. MTT method was used to detect HEL cell proliferation.The apoptotic rate and cell cycle were measured by flow cytometry.The results showed that gefitinib could significantly inhibit the proliferation of HEL cells in a dose-dependent manner,it′s correlation coefficients for 24 and 48 h were 0.991 and 0.895 respectively. IC50 at 48 h was 5.4 μmol/L.Gefitinib could effectively induce apoptosis of HEL cells in a dose-dependent manner（r=0.896）.Otherwise,gefitinib could arrest HEL cells at G0/G1 phase.The inhibitory effect of lapatinib was less than gefitinib,it′s IC50 of inhibiting proliferation of HEL cells was 19.6 μmol/L.It is concluded that both gefitinib and lapatinib can inhibit the proliferation of HEL cells.These two tyrosine kinase inhibitors can be used for researching of targeted therapy of JAK2 V617 positive MPD.