Inhibitory effect of antisense oligodeoxynucleotides complementary to HBV on HepG2.2.15 cell line

doi:10.3748/wjg.v6.iSuppl3.121

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Sep 15, 2000 (publication date) through Dec 3, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Sep 15, 2000; 6(Suppl3): 121-121
Published online Sep 15, 2000. doi: 10.3748/wjg.v6.iSuppl3.121

Inhibitory effect of antisense oligodeoxynucleotides complementary to HBV on HepG₂.2.15 cell line

Chun-Hong Ma, Wen-Seng Sun, Li-Ning Zhang, Pei-Fang Ding

Chun-Hong Ma, Wen-Seng Sun, Li-Ning Zhang, Pei-Fang Ding, Department of Immunology, Shandong Medical University, Jinan 250012, Shandong Province, China

Author contributions: All authors contributed equally to the work.

Supported by National Natural Scientific Foundation, No. 39970333

Correspondence to: Dr. Wen-Sheng Sun, Department of Immunology, Shandong Medical University, Jinan 250012, Shandong Province, China

Telephone: 531-5942038

Received: May 12, 2000
Revised: June 28, 2000
Accepted: July 10, 2000
Published online: September 15, 2000

Abstract

AIM: To explore the therapeutic potential of antisense oligodeoxynucleotides on hepatocellular carcinoma (HCC).

METHODS: Four antisense phosphorothioated oligodeoxynucleotides (asON), complementary to different sites of HBV, were synthesized and assayed for their anti-HBV activity in HepG₂.2.15 cells with ELISA. The most effective asON was chosen for the following study: FACSCAN, TRAP and immuno-staining were used respectively for checking apoptosis, telomerase activity and expression of oncogene p21^ras and p62^C-myc in HepG₂.2.15 cells after treated by asON.

RESULTS: The oligomer directed against the initiator of pre-S2 was the most effective one with an inhibitory rate of 66% on HBsAg and 91% on HBeAg (p < 0.02). Two inhibitory peaks (bimodal) appeared. Telomerase activity as well as the expression of p21^ras and p62^C-myc decreased drastically 3 d after as ON-HbpreS-2 treatment. Meanwhile, apoptosis appeared in the experiments.

CONCLUSION: The inhibitory effects of as-preS₂ on the HBV gene expression and the reversion of some malignant behaviour in HepG₂.2.15 cells were the significant, effective therapy against HBV infection and hepatocellular carcinoma.

Keywords: Liver neoplasms; Hepatitis B virus; Oligonucleotides, antisense; Transfection; Apoptosis; Flow cytometry; Gene expression; Gene therapy