[Effect of tetrandrine, toremifene and their combination on the reversion of multidrug resistance of K562/A02 cell line].
This study was aimed to investigate the reversible effect of tetrandrine, toremifene and their combination on multidrug resistance of K562/A02 cell line. The IC(50) (the concentration causing 50% inhibition of cell growth) of adriamycin (ADR) were assayed by MTT method, the expression of MDR1 mRNA was measured by RT-PCR, the concentration of p-glycoprotein (P-gp) and intracellular ADR were detected by flow cytometry. The results showed that the IC(50) of ADR on K562/A02 and K562 cells were 57.43 and 1.16 mg/L, respectively. The IC(50) of ADR on K562/A02 cells after treatment with tetrandrine, toremifene and both combination were 14.12, 20.74 and 9.14 mg/L respectively, but both drugs did not influence the IC(50) of ADR on K562 cells. Pretreating K562/A02 cells with toremifene (2.5 micromol/L), tetrandrine (1 micromol/L) or both for 72 hours partially restored the sensitivity of K562/A02 cells to ADR. Tetrandrine and toremifene (alone or combination) elevated the ADR concentration in K562/A02, down regulated the expressions of P-gp and MDR1 mRNA. It is concluded that multidrug resistance of K562/A02 cells can be partially reversed by tetrandrine or toremifene, the combination of both drugs shows a higher synergistic reversal effect.
Zhao
Qiu-Xia
QX
Department of Hematology, Zhongda Hospital, Southeast University Clinical Medical College, Nanjing 210009, Jiangsu Province, China.
Chen
Bao-An
BA
Cheng
Jian
J
Ding
Jia-Hua
JH
Gao
Feng
F
Gao
Chong
C
Sun
Yun-Yu
YY
Wang
Jun
J
Zhao
Gang
G
Bao
Wen
W
Song
Hui-Hui
HH
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000494:pharmacology*; D004317:Doxorubicin; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D020014:K562 Cells; D017312:Toremifene / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; C009438:tetrandrine; D017312:Toremifene; D004317:Doxorubicin