S-1, an oral fluoropyrimidine anti-cancer agent, enhanced radiosensitivity in a human oral cancer cell line in vivo and in vitro: involvement possibility of inhibition of survival signal, Akt/PKB.
To examine the effect of an oral fluoropyrimidine anti-cancer agent (S-1) on the radiosensitivity of a human oral cancer cell line with focusing on inhibition of survival signal, Akt/PKB. A human oral cell cancer cell line B88 was used. Activation of Akt/PKB in vivo was examined by immunohistochemistry, and apoptotic cells were detected by TUNEL method. Activation of Akt/PKB in vitro was investigated by Western blot and ELISA, and apoptotic cells were detected by Hoechst 33258 staining. S-1 (10 mg/kg/day or 50 microg/ml) greatly enhanced radiosensitivity in B88 cells by suppressing the activation of Akt/PKB. Significant increase in the percentage of apoptotic cells was observed in S-1 treated B88 cells. Survival signals Akt/PKB may be involved in determining radiosensitivity. S-1, an oral fluoropyrimidine anti-cancer agent can exert the enhancing effect on radiation by suppressing the activation of Akt/PKB.
Harada
Koji
K
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. harako@dent.tokushima-u.ac.jp
Kawaguchi
Shin-ichi
S
Supriatno
Kawashima
Yuichiro
Y
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004338:Drug Combinations; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D010094:Oxonic Acid / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D005641:Tegafur / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D011838:Radiation-Sensitizing Agents; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt