[Using protein chips to study mechanism underlying reversion of drug resistance in leukemia cells in tetrandrine alone or in combination with droloxifene].
The aim of this study was to investigate the mechanism to reverse the drug resistance of leukemia cells in tetrandrine (Tet) alone or in combination with droloxifen (Drol) by using protein chips and to lay the theoretical basis for the clinical applications. Three monoclonal antibodies against P-glycoprotein (P-gp), the multidrug resistance-associated protein (MRP1) and the breast cancer resistance protein (BCRP) were immobilized onto the agarose gel film-coated glass slides. Protein chips were prepared respectively from K562/A02 cells cultured for 12, 24 and 48 hours with Tet alone or in combination with Drol. The results showed that Tet alone or in combination with Drol could decrease only the expression of P-gp in a time-dependent manner, the effect for 48 hours as follows: Tet + Drol 82.620 +/- 3.227; Tet alone 86.440 +/- 2.906; Drol alone 87.230 +/- 2.049; control 93.670 +/- 2.748 (P < 0.05). However, down-regulation of P-gp by K562/A02 cells cultured with Tet alone or in combination with Drol began at 24 hours (Tet + Drol 85.270 +/- 3.095; control 93.670 +/- 2.748, P < 0.05). The results were coincident with that of FCM. It is concluded that Tet and Drol can downregulate the expression of P-gp in the time-dependent way. There is a significant difference between Tet alone and Tet combined with Drol at 24 hours (P < 0.05). The expression of MRP1 and BCRP are not closely correlated with the reversal mechanism of Tet and Drol, and which may be involved in the mechanism of this combination to reverse multidrug resistance in leukemia.
Chen
Bao-An
BA
Department of Hematology, Zhongda Hospital, Southeast University Medical College, Nanjing 210009, China. cba8888@hotmail.com
Du
Juan
J
Zhang
Chun-Xiu
CX
Cheng
Jian
J
Gao
Feng
F
Lu
Zu-Hong
ZH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D040081:Protein Array Analysis; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D013629:Tamoxifen; C116614:ABCG2 protein, human; C038345:droloxifene; C009438:tetrandrine; C421109:multidrug resistance-associated protein 1