CDC25A inhibition suppresses the growth and invasion of human hepatocellular carcinoma cells.
CDC25A is a cell cycle-activating phosphatase that promotes transition from the G1 to S phase. We previously reported that overexpression of CDC25A in human hepatocellular carcinoma (HCC) tissue samples was associated with poor prognosis. In this study, we attempted suppression of CDC25A in HCC cells to elucidate the therapeutic potential of this approach. Administration of CDC25A antisense (AS) oligonucleotide resulted in 25-50% inhibition of cell growth at 48 h, G0-G1 arrest, and significant inhibition of cancer cell invasion. To elucidate the underlying mechanism of the inhibitory effects of HCC cell invasion, we examined several invasion-associated molecules, and we found that membrane-type 3 (MT3)-matrix metalloproteinase (MMP) mRNA was greatly reduced following treatment with AS oligonucleotide to CDC25A or siRNA treatment. Notably, screening of a panel of gastrointestinal cancer cells indicated that MT3-MMP was generally expressed by HCC cells, whereas other cell types did not express this type of matrix metalloproteinase so frequently. We also found that CDC25A facilitated cellular differentiation by increasing albumin expression in the PLC cell line. These results suggest that CDC25A, by inhibiting HCC growth and invasion, may be a feasible therapeutic target for human HCC.
Xu
Xundi
X
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Yamamoto
Hirofumi
H
Liu
Guoxing
G
Ito
Yasuhiro
Y
Ngan
Chew Yee
CY
Kondo
Motoi
M
Nagano
Hiroaki
H
Dono
Keizo
K
Sekimoto
Mitsugu
M
Monden
Morito
M
D000418:Albumins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
D000418:Albumins; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D020687:cdc25 Phosphatases; D020782:Matrix Metalloproteinases; D016650:Fluorescein-5-isothiocyanate