Suppression of tumorigenicity of human hepatocellular carcinoma cells by antisense oligonucleotide MZF-1.
Our previous studies have found that reducing expression of myeloid zinc finger-1 (MZF-1) inhibited protein kinase C alpha (PKCalpha) expression and decreased cell migration and invasion in human hepatocellular carcinoma (HCC). In this study, we further investigated the role of MZF-1 in tumorigenesis. The SK-Hep-1 HCC cells were transfected with the antisense oligonucleotide (ODN) of MZF-1. The pretreated cells was then detected the mRNA and protein levels by RT-PCR and western blotting, and the cell growth was assayed by MTT. Meanwhile, the pretreated-SK-Hep-1 HCC cells were implanted subcutaneously into nude mice to observe the tumor growth and calculated tumor inhibitory rate. The results showed that, at the dosage of 5 microM, the antisense ODN MZF-1 suppressed both MZF-1 and PKCalpha productions by SK-Hep-1 HCC cells after cationic liposome-mediated transfection, to 15% and 30% in control cultures of 0 microM dosage, respectively. The growth of SK-Hep-1 HCC cells was inhibited by the 2-5 microM doses of the antisense ODN MZF-1, whereas the control reagent, the sense ODN MZF-1, showed no effects. In BALB/nude mice, SK-Hep-1 HCC cells pretreated with the 5 microM antisense ODN MZF-1 formed tumors much smaller than the cells with sense ODN. The mean of inhibitory rate of tumor growth was 71.2 +/- 8.6%, and the tumor formation time was prolonged from 14 days to 26 days. These findings suggested the usefulness of antisense ODN MZF-1 as a new reagent for cancer therapy.
Hsieh
Yi-Hsien
YH
Institute of Biochemistry and Biotechnology, Chung-Shan Medical University, Taichung, Taiwan, ROC.
Wu
Trang-Tiau
TT
Huang
Chih-Yang
CY
Hsieh
Yih-Shou
YS
Liu
Jer-Yuh
JY
D000818:Animals; D015197:Carcinogenicity Tests; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D014162:Transfection
D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; D016376:Oligonucleotides, Antisense