Matsubara Akio, Teishima Jun, Mirkhat Suichinov, Yasumoto Hiroaki, Mochizuki Hideki, Seki Mitsuhiro, Mutaguchi Kazuaki, Mckeehan Wallace L, Usui Tsuguru
Department of Urology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Anticancer Res. 2008 Jul-Aug;28(4B):2141-6.
This study was undertaken to investigate the radiosensitizing effects of fibroblast growth factor receptor 2IIIb (FGFR2IIIb) in androgen-independent human prostate carcinoma PC-3 cells devoid of normally resident epithelial cell FGFR2IIIb.
A clonal line of PC-3 cells expressing FGFR2IIIb was established by stable transfection. Clonogenic cell survival, apoptosis and cell cycle distribution with and without gamma-irradiation were then compared between FGFR2IIIb-expressing PC-3 cells and control cells mock-transfected with vector alone.
Gamma-irradiation resulted in an increase of clonogenic cell death concurrent with enhanced apoptosis and cell cycle arrest in the G2/M-phase in both transfected and untransfected cells. A quantitative analysis of all three parameters indicated that cells expressing FGFR2IIIb were significantly more sensitive to irradiation than control cells.
These results indicate that restoration of FGFR2IIIb to PC-3 cells enhances their sensitivity to irradiation through acceleration of apoptosis and cell cycle arrest.
本研究旨在探讨成纤维细胞生长因子受体2IIIb(FGFR2IIIb)对缺乏正常驻留上皮细胞FGFR2IIIb的雄激素非依赖性人前列腺癌PC-3细胞的放射增敏作用。
通过稳定转染建立表达FGFR2IIIb的PC-3细胞克隆系。然后比较表达FGFR2IIIb的PC-3细胞与仅用载体进行模拟转染的对照细胞在有无γ射线照射情况下的克隆形成细胞存活率、凋亡情况和细胞周期分布。
γ射线照射导致转染和未转染细胞的克隆形成细胞死亡增加,同时凋亡增强且细胞周期停滞于G2/M期。对所有三个参数的定量分析表明,表达FGFR2IIIb的细胞对辐射的敏感性明显高于对照细胞。
这些结果表明,将FGFR2IIIb恢复至PC-3细胞可通过加速凋亡和细胞周期停滞来增强其对辐射的敏感性。