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[Survivin antisense oligodeoxynucleotides inhibits the proliferation of hepatocellular carcinoma cells and enhances 5-FU sensitivity].
- Source :
-
Nan fang yi ke da xue xue bao = Journal of Southern Medical University [Nan Fang Yi Ke Da Xue Xue Bao] 2010 Feb; Vol. 30 (2), pp. 304-7. - Publication Year :
- 2010
-
Abstract
- 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.<br />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.<br />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.<br />Conclusion: 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.
- Subjects :
- Animals
Antimetabolites, Antineoplastic pharmacology
Antimetabolites, Antineoplastic therapeutic use
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Cell Line, Tumor
Cell Proliferation drug effects
Drug Synergism
Female
Fluorouracil therapeutic use
Inhibitor of Apoptosis Proteins pharmacology
Inhibitor of Apoptosis Proteins therapeutic use
Liver Neoplasms, Experimental drug therapy
Male
Mice
Oligodeoxyribonucleotides, Antisense therapeutic use
Repressor Proteins pharmacology
Repressor Proteins therapeutic use
Survivin
Fluorouracil pharmacology
Inhibitor of Apoptosis Proteins genetics
Liver Neoplasms, Experimental pathology
Oligodeoxyribonucleotides, Antisense pharmacology
Repressor Proteins genetics
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1673-4254
- Volume :
- 30
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nan fang yi ke da xue xue bao = Journal of Southern Medical University
- Publication Type :
- Academic Journal
- Accession number :
- 20159707