[Targeting delivery effect of galactose receptor-mediated c-myc antisense oligonucleotide on human hepatocellular carcinoma cell line Bel-7402].

Abstract

BACKGROUND & OBJECTIVE:

Deliveries of c-myc antisense oligonucleotide (ASODN) mediated by liposome or adenvirus could suppress proliferation of human hepatocellular carcinoma cells, and tumor growth of mice hepatoma model. However, these deliveries lack targeting effects. Receptor-mediated drug delivery is being used in gene and ASODN delivery due to its high targeting efficiency. This study was to evaluate targeting delivery effect of c-myc ASODN mediated by galactose-polyethyleneimine (Gal-PEI) on human hepatocellular carcinoma cell line Bel-7402.

METHODS:

Bel-7402, and lymphoma cell lines, U937 and Raji, were cultured with fluorescence-labeled Gal-PEI-c-myc ASODN, and c-myc ASODN. The uptaking rates of Gal-PEI-c-myc ASODN, and intracellular mean fluorescence intensities of Bel-7402 and U937 cells were tested by flow cytometry. Morphology of Gal-PEI-c-myc ASODN and c-myc ASODN entering Bel-7402, U937, and Raji cells was observed under phase-contrast fluorescence microscope. Effects of Gal-PEI-c-myc ASODN of various concentrations on proliferation of these cells were detected by trypan blue dye method.

RESULTS:

After cultured for 10 min to 4 h, the uptaking rate, and intracellular mean fluorescence intensity of Gal-PEI-c-myc ASODN cultured Bel-7402 cells (88.25%-98.66%, and 38.61%-111.9%) were higher than those of c-myc ASODN cultured Bel-7402 cells, and Gal-PEI-c-myc ASODN cultured U937 cells, significant differences were detected by Poisson test (P < 0.01). Observed by phase-contrast fluorescence microscope, Gal-PEI-c-myc ASODN entered Bel-7402 cells effectively, but can't enter U937, and Raji cells effectively at the same concentration. C-myc ASODN can't enter Bel-7402 cells effectively at the same ASODN concentration. After incubation with Gal-PEI-c-myc ASODN (containing 0.25-1.25 micromol/L of c-myc ASODN) for 48 h, proliferation of Bel-7402 cells was significantly inhibited (P < 0.01=, but no significant differences were detected in U937, and Raji cells (P >0.05).

CONCLUSION:

Gal-PEI-c-myc ASODN has high targeting delivery effect on Bel-7402 cells, which enhances the intercellular concentration of c-myc ASODN effectively, but it has no such effects on U937, and Raji cells.

• Authors: Jian-Wei Jiang, Yuan Zhang
• Journal: Ai zheng = Aizheng = Chinese journal of cancer (Ai Zheng) Vol. 23 Issue 11 Pg. 1288-93 (Nov 2004) China
• PMID: 15522175 (Publication Type: Comparative Study, English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oligonucleotides, Antisense
• Polyethyleneimine
• Galactose

Topics

• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Delivery Systems (methods)
• Galactose (metabolism)
• Genes, myc (genetics)
• Humans
• Liver Neoplasms (metabolism, pathology)
• Lymphoma (metabolism, pathology)
• Oligonucleotides, Antisense (administration & dosage, pharmacology)
• Polyethyleneimine (metabolism)