抗耐药肿瘤新药PHⅡ-7作用机制的初步研究  

Preliminary Studies on the Mechanisms of a New Anti-tumor Agent PHⅡ-7 with Special Preference to Multidrug Resistant Tumor Cells

作　　者：谭耀红[1] 齐静[1] 刘卫军 杨纯正[1] 

机构地区：[1]中国医学科学院中国协和医科大学血液学研究所实验血液学国家重点实验室,天津300020

出　　处：《中国医学科学院学报》2002年第2期134-139,共6页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(39870860);国家"九五"科技攻关项目(96-906-01-23)资助

摘　　要：目的测定抗耐药肿瘤新药PHⅡ-7体外抗肿瘤谱,初步研究其抗肿瘤机制。方法用MTT法测定PHⅡ-7体外抗肿瘤活性,用流式细胞仪、电子显微镜和琼脂糖凝胶电泳观察PHⅡ-7对肿瘤细胞凋亡的诱导作用,用Northern印迹分析检测PHⅡ-7对耐药相关基因mdr1和sorcin的影响。结果PHⅡ-7对多种人肿瘤细胞的生长有抑制作用,IC50为0.34～18.61μmol/L,更为突出的是,对于MDR类抗肿瘤药无效的多药耐药肿瘤细胞,PHⅡ-7同样具有生长抑制作用;1μg/ml的PHⅡ-7可诱导HL60、HL60/ADR细胞凋亡;PHⅡ-7可抑制K562/A02细胞中耐药相关基因的表达。结论PHⅡ-7是一种有较好前景的抗耐药肿瘤新药,其可能通过抑制耐药相关基因mdr1和sorcin的表达而提高多药耐药细胞内药物浓度,从而引起肿瘤细胞凋亡。Objective To determine the anti-tumor activity of PHⅡ-7 in vitro and explore preliminarily its mechanisms.Methodes The anti-tumor activity was measured using colorimetric MTT assay.Apop-tosis was determined with fluorescence-activated cell sorter(FACS),electron microscopy and agarose gel electrophoresis.The expressions of mdr1and sorcin genes were determined by Northern blot as-say.Results PHⅡ-7inhibited the proliferation of various human tumor cells derived from different tumor cell lines.The IC 50 values varied from0.34～18.61μmol/L.Especially,PHⅡ-7had strong inhibitory effect on multidrug resistant tumor cells,whereas adriamycin(ADR)was resistant.Apoptosis was induced in HL60and HL60/ADR cells treated with1μg/ml PHⅡ-7,while PHⅡ-7inhibited the expressions of mdr1and sorcin genes.Conclusions PHⅡ-7is a new potential agent which has strong inhibitory effect on both multidrug resistant cells and their parental cells.PHⅡ-7may increase the intracellular drug concentration in MDR cells by inhibiting the expressions of the MDR-related genes mdr1and sorcin and induce the apoptosis of MDR cells and their parental tumor cells.

关 键 词：氧化吲哚衍生物 多药耐药 肿瘤细胞株 凋亡 SORCIN 

分 类 号：R979.1[医药卫生—药品]