[Reversal of the multidrug resistance in human hepatocellular carcinoma cells by recombinant adenoviral delivery of the MRP antisense RNA in vitro].
OBJECTIVE
To explore the effect of multidrug resistance-associated protein (MRP) antisense RNA mediated by recombinant adenoviruses on reversal of the multidrug resistance in human drug-resistant hepatocellular carcinoma (HCC) cells.


METHODS
The HCC cells were first treated in vitro by the recombinant adenoviruses containing antisense MRP. Chemosensitivity of all of the cells to ADM and DNR was determined by MTT assay. The levels of the MRP mRNA and its product P190 were measured by RT-PCR and flow cytometry (FCM) respectively according to the time after transfection. The accumulation of the DNR in these cells was analyzed by FCM simultaneously.


RESULTS
IC50 of the cells infected by Ad-Asmrp to ADM and DNR was 0.487 microg/ml and 0.328 microg/ml respectively, with the factors of resistance (RF) decreased by 36.8 and 35.4 respectively (P < 0.05). Continuous decrease in levels of MRP mRNA and P190 was observed 24 h and 48 h after infection respectively (P < 0.01). The intracellular DNR accumulation was increased simultaneously in the Ad-Asmrp transfectants (P < 0.001).


CONCLUSIONS
MRP antisense RNA mediated by recombinant adenoviruses could increase chemosensitivity and partially reverse the MDR in HCC cells in vitro by inhibit expression of MRP gene. The study would provide experimental basis for the reversal of MDR in HCC by antisense RNA technology mediated by recombinant adenoviruses.
Chen
Lin
L
Department of the General Surgery, First Affiliated Hospital, NanJing Medical University, Nanjing 210029, China.
Yan
Lü-nan
LN
Gou
Xing-hua
XH
Li
De-hua
DH
Han
Lei
L
D000256:Adenoviridae / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics; D014162:Transfection
D003630:Daunorubicin; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016372:RNA, Antisense