[Survivin antisense oligodeoxynucleotides inhibits the proliferation of hepatocellular carcinoma cells and enhances 5-FU sensitivity].
OBJECTIVE
To investigate the inhibitory effect of survivin antisense oligodeoxynuleotides (ASODN) mediated by polyethylenimine (PEI) on hepatocelluar carcinoma SMMC-7721 cell proliferation and its effect on chemosensitivity to 5-FU in tumor-bearing mice.


METHODS
The inhibitory effect of PEI-ASODN on SMMC-7721 cell proliferation was assayed by WST-8 test, Trypan blue exclusion test, and cell clone formation assay. In mouse models of transplanted H22 cell hepatocarcinoma and ascites tumor, the effect of 5-FU combined with PEI-ASODN on the weight and volume of the subcutaneous tumors was examined. The tumor inhibition rate in the tumor-bearing mice was calculated and the average survival time recorded.


RESULTS
SMMC-7721 cells incubated with different concentrations of PEI-ASODN for 48 h showed significantly reduced cell proliferation in comparison with the control cells, while PEI or ASODN alone produced no such inhibitory effect. Incubation of SMMC-7721 cells with 0.75 micromol/L PEI-ASODN for 24, 48, 72, and 96 h resulted in significantly suppressed cell proliferation, and a 7-day incubation of the cells with PEI-ASODN at different concentrations (0.25-0.75 micromol/L) significantly inhibited the cell clone formation. In the tumor-bearing mice, the tumor weight and volume were obviously reduced with a tumor inhibition rate of 56.91% and volume inhibition rate of 57.83%, significantly different from those in saline-treated mice (P<0.01). In the mice bearing ascites tumor, the average survival time was 22.0 days in saline group and 42.7 days in 5-FU+PEI-ASODN treatment group, showing a a life-prolonging rate of 94.09% in the latter group. A synergetic effect was noted between 5-FU and PEI-ASODN.


CONCLUSIONS
PEI-ASODN complex can significantly inhibit the proliferation of hepatocarcinoma SMMC-7721 cells and enhance 5-FU chemosensitivity of the tumor cells in vitro and transplanted H22 tumors in mice.
Department of Biochemistry, Medical College of Jinan University, Guangzhou 510630, China. wufengyuncn@126.com
Fen-yun
FY
Wu
Guang-shen
GS
Huang
Jian-wei
JW
Jiang
Fang
F
Wang
Xiang-dong
XD
Xu
Dan-yi
DY
Peng
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D012097:Repressor Proteins / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use; D000077022:Survivin
D000964:Antimetabolites, Antineoplastic; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012097:Repressor Proteins; D000077022:Survivin; D005472:Fluorouracil