Possibility of paclitaxel as an alternative radiosensitizer to 5-fluorouracil for colon cancer.
To evaluate the feasibility of paclitaxel (PTX) radiosensitization for colon cancer, we investigated the cytotoxic and G2/M checkpoint protein (Chk1, Wee1, Bub1, MAD2) effects of 5-fluorouracil (5-FU) or PTX combined with radiation in the human colon cancer cell line LoVo. Cytotoxicity and radiocytotoxicity were evaluated for each drug by the WST-8 colorimetric assay. The IC20 for each drug was determined as a cytotoxic concentration from a survival curve. LoVo cells were exposed to the IC20 of each drug for 24 h and then irradiated. Expressions of the G2/M checkpoint proteins were confirmed by Western blot analysis. Cytotoxicity was induced by 5-FU or PTX alone in a time- and dose-dependent manner. The IC20 of PTX caused higher radiosensitivity than the IC20 of 5-FU (P<0.05). Western blot analysis revealed different expression patterns of the G2/M checkpoint proteins between 5-FU and PTX pre-treatments. 5-FU combined with radiation tended to decrease the expressions of all G2/M checkpoint proteins in a time-dependent manner. PTX combined with radiation maintained high expressions of Chk1 and MAD2 proteins for 24 h post-radiation and, in particular, MAD2 protein was strongly induced by PTX with high-dose radiation. PTX showed higher radio-sensitization than 5-FU for the colon cancer cell line LoVo and may be an alternative radiosensitizer to 5-FU in the clinical setting.
Hiro
Junichiro
J
Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie 514-8507, Japan.
Inoue
Yasuhiro
Y
Toiyama
Yuji
Y
Yoshiyama
Shigeyuki
S
Tanaka
Koji
K
Mohri
Yasuhiko
Y
Miki
Chikao
C
Kusunoki
Masato
M
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel; D005472:Fluorouracil