[Reversal of adriamycin resistance of hepatocellular carcinoma by targeting it with recombined adenovirus carrying antisense multidrug resistance gene 1 RNA].
OBJECTIVE
To investigate if an adenovirus vector carrying antisense multidrug resistance gene 1 (MDR1) could reverse multidrug resistance (MDR) of HepG2/ adriamycin (ADM) cells in tumors transplanted in athymic mice.


METHODS
An adenovirus vector carrying AFP promoter and antisense MDR1 was constructed. HepG2 MDR cells (HepG2/ADM) were induced by graded resistance to ADM and were subcutaneously inoculated into athymic mice to construct the transplanted tumor. After adeno-asmdr1 was injected, the volume of the transplanted tumor and the apoptotic body in the xenograft tumor cells were observed and reverse transcriptase polymerase chain reaction was employed to investigate the expression of the mdr1-mRNA from the mouse transplanted tumor cells.


RESULTS
Following injection with adeno-asmdr1, the tumor volumes in this mice group did not increase. However the tumor volume in the PBS plus ADM group did increase significantly (P less than 0.05). In the tumor xenograft cells, mdr1 mRNA in the xenografts was assessed by RT-PCR and found to be reduced at week 1, and at week 4 in the ADM+asmdr1 group, but it was stable in the ADM group. It was only 20% in the ADM+asmdr1 group compared to the ADM group at the 4th week. Evidence of apoptosis was observed in the tumor xenograft cells treated with adeno-asmdr1, but there was rarely any apoptosis in the group treated with ADM and PBS.


CONCLUSIONS
Adenovirus carrying antisense mdr1 RNA can partially reverse the MDR of HepG2/ADM cells and inhibit tumor growth by down-regulating mdr1 mRNA resulting in tumor cell apoptosis.
Mei
Ying
Y
Second Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400010, China.
Shi
Yu-jun
YJ
Ding
Xiong
X
Wu
Chuan-xin
CX
Jian
Hua-gang
HG
Gong
Jian-ping
JP
Liu
Chang-an
CA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005822:Genetic Vectors; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016372:RNA, Antisense / Q000235:genetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016372:RNA, Antisense; D004317:Doxorubicin