Tabuchi Satoshi, Ozawa Soji, Koyanagi Kazuo, Shigematsu Naoyuki, Kubo Atsushi, Ueda Masakazu, Kitagawa Yuko, Kitajima Masaki
Departments of Surgery and.
Exp Ther Med. 2011 Jul;2(4):601-606. doi: 10.3892/etm.2011.263. Epub 2011 May 10.
Esophageal squamous cell carcinoma (ESCC) is more sensitive to radiation and chemotherapy than other cancers of the digestive system, and combined modality therapy may represent a promising treatment method. The radiation-sensitizing effect of docetaxel on ESCC cell lines was investigated. A colony formation assay was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to docetaxel (from 1.0×10(-11) to 10(-7) M) for 3 h to determine the concentration of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal concentration). Individual cell lines were then exposed to the non-cytocidal concentration of docetaxel prior to, during, and after irradiation to determine whether the timing of docetaxel administration affected cell survival. In addition, flow-cytometry was performed, and the cell cycle was examined prior to and after docetaxel exposure to assess the mechanism of docetaxel as a radiation sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with a different IC(50) for each cell type. Almost no cytocidal effect was observed at the following docetaxel concentrations: A431, ≤1.0×10(-10) M; TE-2 and TE-3, ≤1.0×10(-9) M. Concurrent treatment with docetaxel and radiation tended to decrease cell survival in all the cell lines compared with docetaxel or radiation alone. Cell survival was lowest when the cells were treated using X-ray irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in all three cell lines, docetaxel exposure increased the G2/M cell fraction with a higher increase in the cell line that exhibited the highest radiosensitivity. This study demonstrated that the administration of docetaxel at a non-cytocidal concentration prior to radiotherapy produced a synergistic cell-killing effect in SCC cell lines.
食管鳞状细胞癌（ESCC）比消化系统的其他癌症对放疗和化疗更敏感，联合治疗可能是一种有前景的治疗方法。研究了多西他赛对ESCC细胞系的辐射增敏作用。进行了集落形成试验，将ESCC细胞系（TE2、TE3）和A431暴露于多西他赛（浓度从1.0×10⁻¹¹到10⁻⁷M）3小时，以确定不能杀死单个细胞的多西他赛浓度（即非细胞毒性浓度）。然后将各个细胞系在照射前、照射期间和照射后暴露于非细胞毒性浓度的多西他赛，以确定多西他赛给药时间是否影响细胞存活。此外，进行了流式细胞术检测，并在多西他赛暴露前后检查细胞周期，以评估多西他赛作为辐射增敏剂的作用机制。多西他赛表现出浓度依赖性的细胞毒性作用，每种细胞类型的半数抑制浓度（IC₅₀）不同。在以下多西他赛浓度下几乎未观察到细胞毒性作用：A431，≤1.0×10⁻¹⁰M；TE - 2和TE - 3，≤1.0×10⁻⁹M。与单独使用多西他赛或放疗相比，多西他赛与放疗同时治疗往往会降低所有细胞系的细胞存活率。当细胞在多西他赛暴露后接受X射线照射时，细胞存活率最低（p<0.05）。流式细胞术显示，在所有三种细胞系中，多西他赛暴露均增加了G2/M期细胞比例，其中放射敏感性最高的细胞系增加幅度更大。本研究表明，放疗前给予非细胞毒性浓度的多西他赛可在SCC细胞系中产生协同细胞杀伤作用。
