[In vivo reversal of multidrug resistance by transduction of human tumor necrosis factor-alpha into drug resistant cell line of choriocarcinoma].
OBJECTIVE
To investigate in vivo reversal of multidrug resistance and biological properties of a drug resistant cell line of choriocarcinoma transduced by human tumor necrosis factor-alpha (TNF-alpha) gene via the establishment of its animal model.


METHODS
Choriocarcinoma cell line JEG-3, drug-resistant choriocarcinoma cell line JEG-3/VP2, and human TNF-alpha-transduced drug-resistant choriocarcinoma cell line JEG-3/VP2/TNF-alpha were injected subcutaneously in the neck of nude mices. Tumor size and weight were routinely measured, tumor histological structure was observed and its chemosensitivity was tested. Expression of multidrug resistance (MDR1) mRNA was investigated using reverse transcription-polymerase chain reaction (RT-PCR) and P-glycoprotein (P-gp) expression was determined by immunohistochemistry with the monoclonal antibody MDR1.


RESULTS
The rate of inoculation for all three tested cell lines was 100%, the latent period was 10 to 14 days. Tumor growth rates and weights were significantly different among three cell lines (P < 0.05), with the lowest in JEG-3/VP2/TNF-alpha cell line. Tumor inhibition rate after treatment with etopside (VP-16) was significantly higher in JEG-3/VP2/TNF-alpha (41.0% - 42.5%) (P < 0.05), compared with JEG-3/VP2 (24.3% - 28%), and similar to JEG-3 (46.7% -47.7%). Transduction and expression of human TNF-alpha in drug-resistant choriocarcinoma cell line JEG-3/VP2 was found to reverse MDR1 on the mRNA and P-gp levels.


CONCLUSIONS
Transduction and expression of human TNF-alpha in drug-resistant choriocarcinoma cell line JEG-3/VP2 can reverse expressions of MDR1 mRNA and P-gp, enhance the susceptibility of the JEG-3/VP2 to the cytotoxic drugs, and lower its tumorigenesis.
Feng
Feng-zhi
FZ
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.
Xiang
Yang
Y
Cui
Zhu-mei
ZM
Liu
Zhi-hua
ZH
Yang
Xiu-yu
XY
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000818:Animals; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha