紫杉醇联合放射线照射对肺腺癌细胞放射增敏作用的研究

目的 探讨化疗药紫杉醇是否对肺腺癌A973细胞有放射增敏作用.方法 取指数生长期的人肺腺癌细胞A973,采用成克隆分析法检测紫杉醇毒性,确定IC10、IC50和IC90剂量作为药物浓度.分析照射前后紫杉醇IC10、IC50和IC90浓度下作用24 h,照射剂最分别为0、1、2、4、6、8、10 Gy时的细胞存活分数,并用多靶单击模型拟合细胞存活曲线.采用流式细胞术分析不同浓度紫杉醇作用0、2、4、6、10、18、24 h,A973细胞周期分布变化.结果 紫杉醇对A973细胞的IC10、IC50和IC90剂量分别为0.5、2.6和8.7 nmol/L.IC10剂量紫杉醇照前给药增敏比为0.97(D0值比)、1.01(D0值比)、1.00(SF2值比),照后给药为0.97、1.02、1.02;IC50剂量照前给药为1.06、129.00、2.61,照后给药为0.94、129.00、2.14;IC90剂量照前给药为1.00、120.00、2.09,照后给药为0.98、120.00、2.09.IC10剂量紫杉醇对A973细胞无明显的G2+M期阻滞作用,而IC50和IC90剂量紫杉醇分别于2和18 h将A973细胞阻滞在G2+M期.结论 紫杉醇对肺腺癌细胞A973产生明显的放射增敏作用,且照射前后给药均有相似的增敏作用,中高浓度剂量联合小剂量X线照射增敏效果最好.

Radiosensitization of paclitaxel in lung adenocarcinoma cells

Objective To explore the radiosensitizatian of paclitaxel in human lung adenocareinoma cells. Methods A human lung adenocarcinoma cell line A973 was used in this study. The cytotoxicity of paclitaxel was investigated by using clonngenic assay to define the IC10,IC50 and IC90. The cells received either radiation(with different doses) alone or paclitaxel administrated before and after irradiation. Cell survival fractions were determined by clonogenic assay. Single hit multi-target model was used to determine survival curve parameters. Flow cytometry was performed to analyze the cell cycle distribution. Results The IC10, IC50 and IC90 of paclitaxel in A973 cells were 0.5,2.6 and 8.7 nmol/L,respectively. According to Do,Dq and SF2 value,the sensitivity enhancement ratio(SER) of IC10 was 0.97,1.01 and 2.00 when paclitaxel was added before irradiation, and 0.97,1.02 and 1.02 when after irradiation ; The SER of IC50 was 1.06,129.00 and 2.61 when paclitaxel was added before irradiation, and 0.94,220. O0 and 2.14 when after irradiation ;The SER of IC90 were 1.00,220. 00 and 2.09 when paclitaxel was added before irradiation,and 0.98,220.00 and 2.09 when after irradiation. The IC10 of paclitaxei failed to increase G2+M arrest of A973 cells.The maximal G2+M accumulation was reached at 2 h and 18 h after IC50 and IC90 of paclitaxel treatment,respectively. Conclusions Paclitaxel is able to enhance the radiation sensitivity of A973 cells. Sequence of treatment is not associated with radiosensitivity. Moderate and high dose of paclitaxel combined with low-dose radiation can produce the best effect of radiosensitiation.