异硫氰酸苯己酯诱导骨髓瘤细胞凋亡的实验研究  

Effect of Phenylhexyl Isothiocyanate on Inducing Apoptosis of Multiple Myeloma Cells In Vitro

作　　者：鹿全意[1] 王昭[1] 刘德龙[1] 

机构地区：[1]厦门大学附属中山医院,福建医科大学厦门中心医院血液科,福建厦门361004

出　　处：《中国实验血液学杂志》2008年第1期89-92,共4页Journal of Experimental Hematology

基　　金：厦门市科技计划资助项目,编号3502Z20077042

摘　　要：为了评价异硫氰酸苯己酯(phenylhexly isothiocyanate,PHI)体外对骨髓瘤细胞RPMI8226增殖和分化的影响,用不同浓度的PHI与RPMI8226细胞共同孵育,用原位末端标记法(TUNEL)检测PHI处理后细胞凋亡,流式细胞术分析PHI处理后的细胞周期变化;以JC-1为探针,检测PHI处理后瘤细胞线粒体膜电位的变化,用定量夹心ELISA方法检测PHI处理后瘤细胞分泌血管内皮生长因子(VEGF)的变化。研究结果显示,PHI在低浓度(0.5μmol/L)时显著抑制瘤细胞增殖,诱导瘤细胞发生凋亡,抑制效应与PHI浓度有关,PHI处理后细胞生长停滞在G0/G1期。用10μmol/LPHI处理瘤细胞48小时后,线粒体去极化和膜电位丢失较对照组增加3-4倍,瘤细胞分泌VEGF显著减少,仅为对照组的35%。结论:PHI在体外能够抑制骨髓瘤细增殖,诱导细胞凋亡;细胞凋亡的发生与线粒体去极化和膜电位丢失有关,PHI抑制瘤细胞VEGF的分泌可能是引起细胞凋亡原因之一,PHI是一种潜在的骨髓瘤的治疗药物。In order to investigate the effects of phenylhexyl isothiocyanate （PHI） on proliferation and apoptosis of multiple myeloma cells RPMI8226 in vitro, the RMPI8226 ceils were co-cultured with PHI at various concentrations; the apoptosis of PHI-treated cells was assayed by TUNEL; the ceil cycle changes of PHI-treated cells were analyzed by FCM; the metochondrial potential changes of PHI-treated ceils were detected by using a potential sensitive dye JC-1 as probe; the VEGF levels secreted from PHI-treated ceils were measured by quantitative sandwich ELISA. The results showed that PHI significantly inhibited RPMI8226 cell proliferation, induced their apoptosis at low concentration （0.5 μmol/L）, the inhibitory effect was related to PHI concentration. PHI-treated ceils were arrested in G0/G1 phase. The RPMI8226 cells showed shift from red fluorescence to green fluorescence in some concnetration-dependent manner, indi- caring increase of mitochondrial depolarization and potential loss by 3 - 4-fold as compared with control, after treated RMPI8226 ceils with 10 μmol/L of PHI for 48 hours, the VEGF level secreted from RMPI8226 ceils significantly decreased, it was 35% of control. It is concluded that the PHI can inhibit cell proliferation, induce ceil apoptosis of RMPI8226, the ceil apoptosis is associated with mitochondrial depolarization and potential loss, the inhibiting VEGF secretion from RMPI8226 ceils by PHI may be one of the reasons causing apoptosis. PHI may be a potential therapeutic drug for multiple myeloma.

关 键 词：异硫氰酸苯己酯 骨髓瘤细胞 细胞凋亡 血管内皮生长因子 

分 类 号：R733.3[医药卫生—肿瘤] R979.1[医药卫生—临床医学]