KT-5720 REVERSES MULTIDRUG-RESISTANCE IN VARIANT S49 MOUSE LYMPHOMA-CELLS TRANSDUCED WITH THE HUMAN MDR1 CDNA AND IN HUMAN MULTIDRUG-RESISTANT CARCINOMA-CELLS

被引：12

作者：

GALSKI, H

LAZAROVICI, P

GOTTESMAN, MM

MURAKATA, C

MATSUDA, Y

HOCHMAN, J

机构：

[1] HEBREW UNIV JERUSALEM, INST LIFE SCI, DEPT CELL & ANIM BIOL, IL-91904 JERUSALEM, ISRAEL

[2] HADASSAH UNIV HOSP, MOLEC BIOL & GENET ENGN UNIT, IL-91240 JERUSALEM, ISRAEL

[3] HEBREW UNIV JERUSALEM, SCH PHARM, DEPT PHARMACOL & EXPTL THERAPEUT, IL-91120 JERUSALEM, ISRAEL

[4] NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA

[5] KYOWA HAKKO KOGYO CO LTD, TOKYO 194, JAPAN

来源：

EUROPEAN JOURNAL OF CANCER | 1995年 / 31A卷 / 03期

关键词：

CHEMOSENSITIZERS; K-252A DERIVATIVES; KT-5720; MDR1; MULTIDRUG RESISTANCE; P-GLYCOPROTEIN; PROTEIN KINASES; PROTEIN KINASE INHIBITORS;

D O I：

10.1016/0959-8049(94)00511-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

T-25-Adh cells, cell variants derived from S49 mouse lymphoma, were transduced with a retrovirus containing the human MDR1 cDNA. The resultant cells (HU-1) are cross-resistant to colchicine, doxorubicin, vinblastine and actinomycin D, and their resistance to colchicine is reversed by verapamil. HU-1 cells were used to screen several protein kinase modulators for their ability to reverse multidrug resistance. Among the tested indole carbazole (K-252a) family of protein kinase inhibitors, only the antibiotic alkaloid KT-5720 (9-n-hexyl derivative of K-252a) could overcome the multidrug resistance of HU-1 cells and KB-V1 human carcinoma cells. Since other protein kinase A, C and G modulators did not reverse multidrug resistance in the tested multidrug-resistant cells, the chemosensitising activity of KT-5720 on these cells is apparently independent of its kinase inhibitory effects. Since KT-5720 fully reversed multidrug resistance at non-toxic concentrations, it might be a candidate for clinical chemosensitisation in combination chemotherapy.

引用

页码：380 / 388

页数：9

共 32 条

[1] THE CELL BIOLOGY OF MULTIPLE-DRUG RESISTANCE [J].