Treatment combining X-irradiation and a ribonucleoside anticancer drug, TAS106, effectively suppresses the growth of tumor cells transplanted in mice.
OBJECTIVE
To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice.


METHODS
Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis.


RESULTS
When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed.


CONCLUSIONS
X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth.
Yasui
Hironobu
H
Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Inanami
Osamu
O
Asanuma
Taketoshi
T
Iizuka
Daisuke
D
Nakajima
Takayuki
T
Kon
Yasuhiro
Y
Matsuda
Akira
A
Kuwabara
Mikinori
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D003131:Combined Modality Therapy; D003562:Cytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D012097:Repressor Proteins; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D000077022:Survivin
C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; D000970:Antineoplastic Agents; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; C498355:Mki67 protein, mouse; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D000077022:Survivin; D003562:Cytidine