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Cell Biology International (2008) 32, 210–216 (Printed in Great Britain)

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Antisense oligonucleotide Elk-1 suppresses the tumorigenicity of human hepatocellular carcinoma cells

Tsung‑Ho Ying^ab, Yi‑Hsien Hsieh^b, Yih‑Shou Hsieh^b and Jer‑Yuh Liu^b*

^aDepartment of Obstetrics and Gynecology, Chung Shan Medical University Hospital, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung 40203, Taiwan
^bInstitute of Biochemistry and Biotechnology, School of Medicine, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung 40203, Taichung, Taiwan

Abstract

In previous studies, we showed that reducing Ets-like protein-1 (Elk-1) expression inhibited protein kinase C alpha (PKCα) expression and decreased cell migration and invasion in human hepatocellular carcinoma (HCC). In this study, we have investigated the role of Elk-1 in tumorigenesis. SK-Hep-1 HCC cells were transfected with the ElK-1 antisense oligonucleotide (ODN). In the pretreated cells we detected a reduction of mRNA level using RT–PCR. The inhibitory rate of cell growth was measured by MTT assay. Pretreated-SK-Hep-1 HCC cells were implanted subcutaneously into nude mice to observe the tumor growth and calculate tumor inhibitory rate. The results showed that 5μM of the antisense ODN Elk-1 suppressed both Elk-1 and PKCα production by SK-Hep-1 HCC cells after cationic liposome-mediated transfection, to 8% and 1% of control values, respectively, and the growth of SK-Hep-1 HCC cells was inhibited at 2–5μM doses of the antisense ODN Elk-1. The control reagent, sense ODN Elk-1, showed no effects. In BALB/nude mice, SK-Hep-1 HCC cells transfected with the 5μM antisense ODN Elk-1 formed tumors much smaller than those of sense ODN Elk-1 pretreated cells. The maximum inhibitory rate of tumor growth was 80.8±12.6% and the tumor formation time was prolonged from 13 to 25days. These findings suggested the usefulness of antisense ODN Elk-1 as a new reagent for liver cancer therapy.

Key words: Elk-1, Hepatocellular carcinoma, Protein kinase C alpha, Tumorigenesis, Antisense oligonucleotide.

^*Corresponding author. Tel.: +886 4 2473 0022x11673; fax: +886 4 2324 8195.

Received 23 April 2007/3 August 2007; accepted 29 August 2007