红霉素及细胞因子逆转白血病细胞耐药性的研究  

STUDY OF ERY、GMCSF、αIFN IN REVERSING THE MDR OF LEUKEMIA CELLS

作　　者：陈同辛[1,2] 林梓[1,2] 周昕[1,2] 伍钢[1,2] 沈蕾[1,2] 应大明[1,2] 

机构地区：[1]上海第二医科大学儿科医学研究所 [2]上海第二医科大学新华医院

出　　处：《白血病》1997年第4期202-207,共6页

摘　　要：利用亲脂性药物Ｅｒｙ单独或与Ｄｏｘ合用处理Ｋ５６２／ＶＣＲ细胞，观察了其对细胞的增殖抑制作用，以及对细胞内Ｄｏｘ浓度的影响，实验结果表明：在无Ｅｒｙ存在下，Ｄｏｘ对Ｋ５６２／ＶＣＲ细胞的增殖抑制作用较小，与Ｅｒｙ合用后可明显地提高Ｋ５６２／ＶＣＲ细胞内Ｄｏｘ的浓度，并可增强Ｄｏｘ对Ｋ５６２／ＶＣＲ细胞的增殖抑制作用。此结果与国外的结果相一致。因而进一步提示了亲脂类药物逆转肿瘤细胞ＭＤＲ的机制可能与其抗肿瘤药物竞争性地与Ｐ－Ｇｐ结合，以减少抗肿瘤药物的外排有关，但是本组实验结果还表明：Ｅｒｙ与Ｄｏｘ合用处理Ｋ５６２／ＶＣＲ细胞对细胞膜Ｐ－Ｇｐ的表达影响较小，提示了亲脂类药物作用于Ｐ－Ｇｐ的位点可能和单克隆抗体结合抗原决定簇不同，故亲脂类药物与Ｐ－ＧＰ结合不影响单克隆抗体与Ｐ－Ｇｐ结合。With the lipophilic drugs such as Erythromycin alone or combination with Doxorubin to treat K562/VCR cells, the proliferative inhibition effect of these drugs on these cells and the effect on the doxorubin level in these cells were studied.The experimental results showed that the effect of doxorubicin on inhibiting the K562/VCR cell proliferation was less, if with no presence of Erythromycin; on the contrary, if erythromycin combined with Doxorubicin, not only could the doxorubicin level in K562/VCR cell be greatly increased, but also significantly enhance the proliferative inhibition effect of Doxorubicin on K562/VCR cells, further indicating that the mechanism of the lipophilic drugs in reversing the MDR of the tumor cells might be related to the comparative integration of the antitumor drugs with the PGP, thus reduced the expellcd level of the antitumor drugs. In addition, our study also indicated that effect on the PGP expression on these cells surface was less when erythromycin was combined with Doxorubicin to treat the K562/VCR cells. Suggesting that the effective location of the lipophilic drugs might be different from that of the antigen determinants which could be integrated with the monoclonal antibodies. So the combination of lipophilic drugs with PGP did not have any effect on the combination of monoclonal antibodies with PGP.

关 键 词：红霉素 白血病细胞 耐药性 细胞增殖率 

分 类 号：R733.705[医药卫生—肿瘤] R73－36[医药卫生—临床医学]