Interferon potentiates antiproliferative activity of CPT-11 against human colon cancer xenografts.
We studied the antiproliferative effect of recombinant human interferon-alpha/beta/gamma (rHuIFN-alpha/beta/gamma) and CPT-11 against human colon cancer xenografts in nude mice. CPT-11 (25 mg/kg) alone exhibited significant antiproliferative effects. Although rHuIFN-alpha/beta/gamma alone did not show antiproliferative activity, it markedly enhanced the antiproliferative activity of CPT-11. rHuIFN-alpha/beta/gamma significantly increased in the population of cells in the S-phase. rHuIFN-alpha/beta/gamma progressed cell cycle in the S-phase under the existence of CPT-11, which exhibited no effect on cell cycle progression. Because CPT-11 is known to exhibit antiproliferative effect on S-phase cells, IFNs, especially rHuIFN-alpha and beta, can enhance the antiproliferative effect of CPT-11 mediated by cell accumulation in the S-phase.
Ohwada
S
S
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan. sohwada@sb.gunma-u.ac.jp
Kobayashi
I
I
Maemura
M
M
Satoh
Y
Y
Ogawa
T
T
Iino
Y
Y
Morishita
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D000077146:Irinotecan; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011994:Recombinant Proteins / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000077146:Irinotecan; D016899:Interferon-beta; D007371:Interferon-gamma; D002166:Camptothecin