[Comparison of reversal effects of 5-bromotetrandrine and tetrandrine on P-glycoprotein-dependent Resistance to adriamycin in human lukemia cell line K562/A02].
OBJECTIVE
5-Bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), could effectively reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). This study was to compare the reversal effects of BrTet and Tet on MDR of human leukemia cell line K562/A02.


METHODS
The effects of BrTet on the proliferation of K562 and K562/A02 cells were observed by MTT assay. The inhibitory effects of adriamycin (ADM) used alone or in combination with BrTet or Tet on the proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The effect of BrTet or Tet on ADM accumulation was analyzed by flow cytometry (FCM). The protein level of P-gp was detected by Western blot.


RESULTS
The inhibition rates of low concentrations of BrTet (< or =2.0 micromol/L) and Tet (< or =1.5 micromol/L) on the proliferation of K562 and K562/A02 cells were below 10%; no significant cytotoxicity was observed. The resistance of K562/A02 cells to ADM was 49.51 folds of that of K562 cells. When added 1.0 micromol/L Tet, the chemosensitivity of K562/A02 cells to ADM was increased to 12.17 folds; when added 0.25, 0.5 and 1.0 micromol/L BrTet, the chemosensitivity of K562/A02 cells to ADM was increased to 17.88, 9.9 and 4.24 folds, respectively. FCM showed that 1.0 micromol/L BrTet inhibited the overexpression of P-gp and increased the accumulation of ADM in K562/A02 cells, and its potency was greater than that of 1.0 micromol/L Tet(P<0.05).


CONCLUSIONS
BrTet could reverse MDR in vitro. Its activity may be related to the inhibition of P-gp overexpression and the increase in intracellular accumulation of anticancer drugs.
Wang
Jue-Qiong
JQ
Department of Hematology, Zhongda Hospital, Southeast University, Nanjing,Jiangsu, 210009, People's Republic of China.
Chen
Bao-An
BA
Cheng
Jian
J
Xu
Wen-Lin
WL
Sun
Xin-Chen
XC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; C514835:bromotetrandrine; C009438:tetrandrine; D004317:Doxorubicin