Modulation of BCRP mediated atypical multidrug resistance phenotype by RNA interference.
Multidrug resistance (MDR) in human cancers is one of the major causes of failure of chemotherapy. The emergence of breast cancer resistance protein (BCRP), a member of the ABC transporter family, has necessitated the development of antagonists. To overcome the BCRP-mediated atypical multidrug drug resistance, two small interfering RNA constructs (RNAi) targeting two different regions of BCRP mRNA were designed to inhibit the atypical MDR expression by transfecting them into MCF-7/MX100 cell lines. The multidrug resistance index to mitoxantrone and the intensity of mitoxantrone fluorescence of MCF-7/MX100 decreased after transfected by pSUPER-BCRP-A and pSUPER-BCRP-B respectively; the BCRP mRNA level and the BCRP protein level of MCF-7/MX100 decreased after treated with pSUPER-BCRPs. The two constructed RNAi plasmids could reverse the atypical mutidrug resistance mediated by BCRP, but neither can reversed it completely, this may be due to low transfection efficiency and transient transfection.
Li
W T
WT
Department of Pathology, Medical School, Shandong University, Jinan, 250012 Shandong Province, P.R.China.
Zhou
G Y
GY
Song
X R
XR
Chi
W L
WL
Ren
R M
RM
Wang
X W
XW
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D003001:Cloning, Molecular; D015536:Down-Regulation; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D008942:Mitoxantrone