[Survivin antisense oligodeoxynucleotides inhibits the proliferation of hepatocellular carcinoma cells and enhances the cell chemosensitivity to 5-Fu].
OBJECTIVE
To investigate the inhibitory effect of survivin antisense oligodeoxynucleotides (ASODN) mediated by polyethylenimine(PEI) on the proliferation of hepatocellular carcinoma SMMC-7721 cells, and assess its detect on the chemosensitivity of the cells to 5-FU.


METHODS
The inhibitory effect of PEI-ASODN on SMMC-7721 cell proliferation was assessed using WST-8 test, trypan blue staining, and cell clone formation test. In mice bearing transplanted hepatocarcinoma and ascites tumor derived from H22 cells, 5-FU combined with PEI-ASODN was administered, and the weight and volume of the subcutaneous tumors were measured to calculate the tumor inhibition rate, and the average survival time of the mice was calculated.


RESULTS
Incubation of the cells with different concentrations of PEI-ASODN for 48 h significantly inhibited the cell proliferation as compared with the control group, but PEI or ASODN alone produced no significant inhibitory effects. At 24, 48, 72, 96 h of incubation of the SMMC-7721 cells with 0.75 micromol/L PEI-ASODN, the cell proliferation was suppressed significantly, and incubation with PEI-ASODN at 0.25-0.75 micromol/L for 7 days resulted in significantly inhibited cell clone formation. No significant inhibition was detected in ASODN and PEI group. The tumor weight and volume were reduced in all the treated groups. The tumor inhibition rate was 56.91% and volume inhibition rate was 57.83% in 5-FU+PEI-ASODN group, significantly different from those in the normal saline group (P<0.01). In mice bearing ascites tumor, the average survival time was 22.0 days in saline group, and 42.7 days 5-FU+PEI-ASODN group. The life-prolongation rate of 5-FU+PEI-ASODN was 94.09% when compared with the survival time in saline group. A cooperative effect was detected between 5-FU and PEI-ASODN.


CONCLUSIONS
PEI-ASODN complex can significantly inhibit the proliferation of hepatocarcinoma SMMC-7721 cells and enhance the chemosensitivity of the tumor cells to 5-FU.
Wu
Fen-Yun
FY
Department of Biochemistry, Medical College of Jinan University, Guangzhou 510630, China. wufengyuncn@126.com
Huang
Guang-Shen
GS
Jiang
Jian-Wei
JW
Wang
Fang
F
Xu
Xiang-Dong
XD
Peng
Dan-Yi
DY
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics / Q000494:pharmacology*; D000077022:Survivin
D000964:Antimetabolites, Antineoplastic; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012097:Repressor Proteins; D000077022:Survivin; D005472:Fluorouracil