Treatment combining X-irradiation and a ribonucleoside anticancer drug, TAS106, effectively suppresses the growth of tumor cells transplanted in mice.

Abstract

PURPOSE:

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 AND MATERIALS:

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.

• Authors: Hironobu Yasui, Osamu Inanami, Taketoshi Asanuma, Daisuke Iizuka, Takayuki Nakajima, Yasuhiro Kon, Akira Matsuda, Mikinori Kuwabara
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 68 Issue 1 Pg. 218-28 (May 01 2007) ISSN: 0360-3016 [Print] United States
• PMID: 17448876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(3-C-ethynylribopentofuranosyl)cytosine
• Antineoplastic Agents
• Birc5 protein, mouse
• Inhibitor of Apoptosis Proteins
• Ki-67 Antigen
• Microtubule-Associated Proteins
• Mki67 protein, mouse
• Neoplasm Proteins
• Repressor Proteins
• Survivin
• Cytidine

Topics

• Adenocarcinoma (drug therapy, metabolism, radiotherapy)
• Animals
• Antineoplastic Agents (therapeutic use)
• Colonic Neoplasms (drug therapy, metabolism, radiotherapy)
• Combined Modality Therapy
• Cytidine (analogs & derivatives, therapeutic use)
• Drug Evaluation, Preclinical
• Female
• Inhibitor of Apoptosis Proteins
• Ki-67 Antigen (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Microtubule-Associated Proteins (metabolism)
• Neoplasm Proteins (metabolism)
• Neoplasm Transplantation
• Repressor Proteins
• Stomach Neoplasms (drug therapy, metabolism, radiotherapy)
• Survivin