Liver Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 1, 2004; 10(3): 366-370
Published online Feb 1, 2004. doi: 10.3748/wjg.v10.i3.366
Antisense oligonucleotide targeting at the initiator of hTERT arrests growth of hepatoma cells
Su-Xia Liu, Wen-Sheng Sun, Ying-Lin Cao, Chun-Hong Ma, Li-Hui Han, Li-Ning Zhang, Zhen-Guang Wang, Fa-Liang Zhu
Su-Xia Liu, Wen-Sheng Sun, Ying-Lin Cao, Chun-Hong Ma, Li-Hui Han, Li-Ning Zhang, Zhen-Guang Wang, Fa-Liang Zhu, Institute of Immunology, Medical School of Shandong University, Wenhua West Road 44, Jinan 250012, Shandong Province, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No.30070341
Correspondence to: Dr. Wen-Sheng Sun, Institute of Immunology, Medical School of Shandong University, Wenhua West Road 44, Jinan 250012, Shandong Province, China. wangjd@jn-public.sd.cninfo.net
Telephone: +86-531-8382038 Fax: +86-531-8382084
Received: September 14, 2002
Revised: October 21, 2002
Accepted: October 28, 2002
Published online: February 1, 2004
Abstract

AIM: To evaluate the inhibitory effect of antisense phosphorothioate oligonucleotide (asON) complementary to the initiator of human telomerase catalytic subunit (hTERT) on the growth of hepatoma cells.

METHODS: The as-hTERT was synthesized by using a DNA synthesizer. HepG2.2.15 cells were treated with as-hTERT at the concentration of 10 μmol/L. After 72 h, these cells were obtained for detecting growth inhibition, telomerase activity using the methods of MTT, TRAP-PCR-ELISA, respectively. BALB/c(nu/nu) mice were injected HepG2.2.15 cells and a human-nude mice model was obtained. There were three groups for anti-tumor activity study. Once tumors were established, these animals in the first group were administered as-hTERT and saline. Apoptosis of tumor cells was detected by FCM. In the 2nd group, the animals were injected HepG2.2.15 cells together with as-hTERT. In the third group, the animals were given as-hTERT 24 hours postinjection of HepG2.2.15 cells. The anti-HBV effects were assayed with ELISA in vitro and in vivo.

RESULTS: Growth inhibition was observed in cells treated with as-hTERT in vitro. A significant different in the value of A570 - A630 was found between cells treated with as-hTERT and control (P < 0.01) by MTT method. The telomerase activity of tumor cells treated with as-hTERT was reduced, the value of A450 nm was 0.42 compared to control (1.49) with TRAP-PCR-ELISA. The peak of apoptosis in tumor cells given as-hTERT was 21.12%, but not seen in saline-treated control. A prolonged period of carcinogenesis was observed in the second and third group animals. There was inhibitory effect on the expression of HBsAg and HBeAg in vivo and in vitro.

CONCLUSION: As-hTERT has an anti-tumor activity, which may be useful for gene therapy of tumors.

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