Cai Yong, Sheng Zhaoying, Dong Zhiyi, Wang Jiying
Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Department of Traditional Chinese Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Curr Mol Pharmacol. 2023;16(2):211-216. doi: 10.2174/1874467215666220329212300.
This study aimed to explore the influence of the irreversible EGFR inhibitor CL-387785 on invasion, metastasis, and radiation sensitization of non-small cell lung cancer cells.
The proliferation inhibitory rate at different time points was detected by MTT assay. The apoptosis of H1975 cells treated with CL-387785 was detected using flow cytometry. The invasion and migration of H1975 cells treated with CL-387785 were determined by Transwell assay and wound healing assay. The survival fraction (SF) of H1975 cells cultured with CL- 387785 under X-ray (0, 2, 4, 6, 8, and 10 Gy) was detected by cloning formation experiment, and the sensitization ratio (SER) was calculated by clicking the multi-target model to fit the cell survival curve.
CL-387785 restrained H1975 cell proliferation in a concentration- and time-dependent manner. CL-387785 promoted H1975 cell apoptosis and reduced cell migration distance and the number of transmembrane cells. The SF treated by different concentrations of CL-387785 (10, 25, 50, and 100 nM) was all below 0 nM. The radiation SER of CL-387785 (10, 25, 50 and 100 nM) were 1.17, 1.39, 2.88, and 3.64, respectively.
The invasion and metastasis of H1975 cells were restrained by irreversible EGFR inhibitor CL-387785. CL-387785 also exhibited the effect of radiotherapy sensitization.
本研究旨在探讨不可逆表皮生长因子受体（EGFR）抑制剂CL-387785对非小细胞肺癌细胞侵袭、转移及辐射增敏的影响。
采用MTT法检测不同时间点的增殖抑制率。运用流式细胞术检测经CL-387785处理的H1975细胞的凋亡情况。通过Transwell实验和划痕实验测定经CL-387785处理的H1975细胞的侵袭和迁移能力。采用克隆形成实验检测在X射线（0、2、4、6、8和10 Gy）照射下经CL-387785培养的H1975细胞的存活分数（SF），并通过点击多靶点模型拟合细胞存活曲线计算增敏比（SER）。
CL-387785以浓度和时间依赖性方式抑制H1975细胞增殖。CL-387785促进H1975细胞凋亡，减少细胞迁移距离和穿膜细胞数量。不同浓度（10、25、50和100 nM）的CL-387785处理后的SF均低于0 nM。CL-387785（10、25、50和100 nM）的辐射SER分别为1.17、1.39、2.88和3.64。
不可逆EGFR抑制剂CL-387785抑制H1975细胞的侵袭和转移。CL-387785还具有放疗增敏作用。
