Downregulation of survivin expression by induction of the effector cell protease receptor-1 reduces tumor growth potential and results in an increased sensitivity to anticancer agents in human colon cancer.
Survivin, a novel inhibitor of apoptosis, is expressed in cancer cells and not in normal adult tissues, and is recognised as a potential target in anticancer therapy. The induction of a natural antisense of survivin, effector cell protease receptor-1 (EPR-1), in a human colon cancer cell line resulted in a downregulation of survivin expression, with a similar decrease in cell proliferation, an increase in apoptosis and an increase in the sensitivity to anticancer agents. In addition, subcutaneous (s.c.) tumours from EPR-1 transfectants showed a significant reduction in size compared with parental cells, and this antitumour efficacy was further enhanced in combination with anticancer agents. These findings suggest that regulation of survivin by the induction of EPR-1 cDNA may have significant potential as a therapy for human colon cancer.
Yamamoto
Tetsuhisa
T
Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, 569-8686, Osaka, Japan.
Manome
Yoshinobu
Y
Nakamura
Motoyuki
M
Tanigawa
Nobuhiko
N
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D018076:DNA, Complementary; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D000077022:Survivin