Kim Jae-Chul, Kim Jae-Sung, Saha Debabrata, Cao Qianwen, Shyr Yu, Choy Hak
Department of Radiation Oncology, The Vanderbilt Clinic B-902, 1003 TVC Vanderbilt University Medical Center, 1301 22nd Avenue South, Nashville, TN 37232-5671, USA.
Radiother Oncol. 2003 Sep;68(3):305-13. doi: 10.1016/s0167-8140(03)00200-7.
To evaluate a semisynthetic epothilone B, BMS-247550, as a potential radiosensitizer in vitro and in vivo.
Human NCI-H460 lung cancer cells were treated with either BMS-247550 or paclitaxel and in combination with radiation at multiple doses for different time periods. Surviving fractions were then analyzed using a clonogenic assay. Cell cycle redistribution by BMS-247550 was measured with propidium iodide and flow cytometry. Percent apoptosis was also measured using 7-amino-actinomycin D staining with flow cytometry. For in vivo studies, the H460 xenograft model was used in athymic nude mice. Tumors were treated with BMS-247550 (5 mg/kg) i.p. injection on days 0, 2, and 4 and/or radiation (2 Gy/day, days 0-4).
The in vitro radiation dose enhancement ratios (DER) of 1-h BMS-247550 and paclitaxel were 2.03 and 1.34, respectively. Treatment with BMS-247550 enhanced the G2/M block and induced apoptosis; whereas in combination with radiation, the induction of apoptosis was additive. BMS-247550 in combination with radiation in vivo enhanced the tumor growth delay when compared with either drug or radiation alone.
These results demonstrated that BMS-247550 could enhance the effects of radiation in human lung cancer cells both in vitro and in vivo and that a G2/M block and increased apoptosis might be possible explanations for the enhancement.
评估半合成埃坡霉素B（BMS - 247550）在体外和体内作为潜在放射增敏剂的效果。
人NCI - H460肺癌细胞分别用BMS - 247550或紫杉醇处理，并在不同时间段与多种剂量的辐射联合使用。然后使用克隆形成试验分析存活分数。用碘化丙啶和流式细胞术测量BMS - 247550引起的细胞周期重新分布。还用7 - 氨基放线菌素D染色和流式细胞术测量凋亡百分比。对于体内研究，在无胸腺裸鼠中使用H460异种移植模型。在第0、2和4天腹腔注射BMS - 247550（5mg/kg）和/或辐射（2Gy/天，第0 - 4天）对肿瘤进行处理。
1小时的BMS - 247550和紫杉醇的体外辐射剂量增强比（DER）分别为2.03和1.34。BMS - 247550处理增强了G2/M期阻滞并诱导了凋亡；而与辐射联合使用时，凋亡诱导是相加的。与单独使用药物或辐射相比，BMS - 247550与辐射联合在体内增强了肿瘤生长延迟。
这些结果表明，BMS - 247550在体外和体内均可增强辐射对人肺癌细胞的作用，G2/M期阻滞和凋亡增加可能是这种增强作用的解释。
