[Reversal of multidrug resistance of human hepatocarcinoma HepG2/Adm cells by high intensity focused ultrasound].
OBJECTIVE
The effects of ultrasound have been shown on increasing cell membrane permeability and thereby might promote cellular uptake of cytotoxic drugs and enhance chemotoxicity. The aim of this study was to examine the reversal effects of high intensity focused ultrasound (HIFU) and co-administration with Adriamycin (ADM) on multidrug resistance (MDR) in HepG2/Adm cells, and to investigate its mechanism.


METHODS
HepG2 cells and HepG2/Adm cells were divided into 4 groups: HepG2 (control group),HepG2 (treated with HIFU 5s),HepG2/Adm (non HIFU), and HepG2/Adm (treated with HIFU 5s). MTT assay was used to examine the chemosensitivity to ADM in HIFU-treated HepG2 and HepG2/Adm cell lines. Before and after the treatment with HIFU 5s, MDR1 gene expression was determined by immunocytochemistry assay. Flow cytometry was used to determine intracellular ADM concentration and the expression of P-gp on cell membranes.


RESULTS
HIFU (0.8MHz, 460W/cm2) partly overcame the MDR of cell line HepG2/Adm and decreased the drug resistance. The relative reverse efficiencies to ADM, cisplatin (DDP), mytomycin (MMC), 5-fluorouracil (5-FU), and methotrexate (MTX) were 66.4%, 63.4%, 89.4%, 72.4%, and 75.0%, respectively. While, the concentration of ADM in HepG2/Adm cells was increased by 88%. The expression of P-glycoprotein (P-gp) protein in HepG2/Adm was down-regulated by 83.1%.


CONCLUSIONS
HIFU can not only increase the ADM concentration in HepG2/Adm cells and decrease P-gp expression on cellular and nuclear membrane, but also partly overcome MDR of tumor cells.
Zhai
Bao-Jin
BJ
The Center for Tumor Therapy, The 2nd Affiliated Hospital, Chongqing University of Medical Science, Chongqing, PR China. zhaibaojin@yahoo.com.cn
Shao
Ze-Yong
ZY
Wu
Feng
F
Wang
Zhi-Biao
ZB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000528:radiation effects*; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D014407:Tumor Cells, Cultured; D014465:Ultrasonics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin