Inhibitory effect of EGFR antisense oligodeoxynucleotide on human hepatoma cell line.
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. The epidermal growth factor receptor (EGFR) is highly expressed in many human tumors and provides a new target for anticancer drug development. The aim of the present study was to explore the effect of EGFR antisense oligodeoxynucleotide on human HCC.


METHODS
SMMC-7721 cells in culture were treated with 10 mumol/L antisense-odn for 24, 48, 72 hours respectively and MTT assay was adopted to determine the proliferation of tumor cells in vitro. About 2 x 10(6) SMMC-7721 cells with or without pretreatment(30 micromol/L oligodeoxynucleotide) were inoculated into subcutaneous flap of 21 nude mice, of which 7 were treated with EGFR antisense-odn, 7 with scrambled oligodeoxynucleotide (scrambled-odn), and 7 not treated in vivo.


RESULTS
In vitro, after 24, 48, 72 hours the inhibitory rate of proliferation of SMMC-7721 cells treated with EGFR antisense-odn was 8%, 32%, and 34% respectively. In vivo after 8 weeks, no palpable tumor was found in 1/7 mice receiving cells pretreated with antisense-odn, whereas 7/7 untreated mice and 6/7 mice treated with scrambled-odn developed palpable tumors. Tumor growth in antisense-odn treated mice was significantly inhibited in comparison with that of those untreated (P < 0.01) or treated with scrambled-odn (P < 0.05).


CONCLUSIONS
Antisense oligodeoxynucleotide acts as a specific growth inhibitor on SMMC-7721 in a sequence specific and time-dependent manner. EGFR antisense-odn can significantly inhibit the proliferation of human hepatoma cell in vitro as well as in vivo, indicating that EGFR may play an important role in the development of hepatoma and will be a new target for its treatment.
Gong
Zhi-Bing
ZB
Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Liu
Jing-Mei
JM
Li
You-Ming
YM
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*
D016376:Oligonucleotides, Antisense; D066246:ErbB Receptors