[TNF-alpha induced reversal of multidrug resistance in human hepatocellular carcinoma cells].
OBJECTIVE
To investigate the reversal of multidrug resistance in the cell line HepG2/ADM induced by TNF-alpha.


METHODS
HepG2/ADM cells were incubated with different concentrations of TNF-alpha (100, 500 and 2500 U/ml) for 72 h. Real-time PCR was performed to compare the mRNA levels of MDR1 with PPAR-alpha in the different concentrations of TNF-alpha treated cells. The Annexin V assay was used to check cell apoptosis induced by 0.5 mg/L adriamycin. Rhodamine 123 efflux assay and MTT assay were used to study P-gp activity and drug resistance in each group, respectively.


RESULTS
TNF-alpha could induce down-regulation of MDR1 and up-regulation of PPAR-alpha. Meanwhile, it could enhance cell cytotoxicity and cell apoptosis induced by 0.5 mg/L adriamycin.


CONCLUSIONS
TNF-alpha could partially reverse the multidrug resistance of HepG2/ADM cells by down-regulating the expression of MDR1 and up-regulating the expression of PPAR-alpha.
Wang
Qi
Q
Department of Hepato-Biliary-Pancreatic Surgery Center, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Chen
Xiao-ping
XP
Hai
Shan
S
Li
Gao-peng
GP
Guan
Jian
J
Zhang
Bi-xiang
BX
Zhang
Wan-guang
WG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D047493:PPAR alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin