摘要
目的:探讨非小细胞肺癌精准放射治疗中,α/β值对区分不同驱动基因分型肺癌细胞的应用价值,同时检测丝氨酸/苏氨酸蛋白激酶抑制剂MK1775对不同基因分型细胞α/β值的影响以及放射增敏或协同作用。方法:分别培养表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变型肺癌PC9细胞、鼠类肉瘤病毒癌基因同源物(V-Kiras2-Kirsten rat sarcoma viral oncogene homolog,K-RAS)基因突变型肺癌A549细胞和p 53基因突变型肺癌H1299细胞,并分成对照组、放射组和MK1775抑制剂联合放射组。单纯放射组和加药放射组均采用能量为6MV、剂量率为3 Gy/min的X射线照射,照射剂量均分为0、0.25、0.5、1、2、3、4、5和6 Gy共9个梯度。采用克隆计数法分析不同放射剂量与细胞存活率之间的量效关系,以及MK1775对3种基因突变型细胞的放射增敏和协同作用。结果:不同的基因突变对应不同的放射超敏剂量。另外,用MK1775抑制剂后,PC9、A549和H1299细胞在X射线照射前的克隆数分别下降为用药前的56.4%、54.5%和73.2%,说明MK1775与放射存在协同作用。除A549细胞外,PC9细胞和H1299细胞在用药前α/β值为负值,而用药后3种细胞的α/β值均为正值,提示MK1775抑制剂仅对α/β值为负值的PC9和H1299细胞放射治疗具有增敏作用。对于不同的驱动基因突变型细胞,加药放射组和单纯放射组之间α.β值均存在明显差异(P值均<0.05)。结论:不同的驱动基因有着不同的α和β值,因而对应着不同的等效生物剂量,而且MK1775对不同基因突变型肺癌细胞的放射增敏或协同效应各不相同。
Objective： To explore the importance of distinguishing α/β values for different lung cancer cells based on driver genes and its significance in the precise radiotherapy. At the same time, to study the influence of serine/threonine kinase inhibitor MK1775 on the α/β values for different kinds of cells and to investigate the radiation sensitization or synergistic effect of MK1775. Methods： Lung cancer PC9 cells with epidermal growth factor receptor （EGFR） gene mutant, A549 cells with V-Ki-ras2-Kirsten rat sarcoma viral oncogene homolog （K-RAS） gene mutant, and H1299 cells with p53 gene mutant were respectively cultured and assigned into three groups： the control group, radiation alone group, and MK1775 inhibitor combined with radiation group. 6 MV X-ray with a dose rate of 3 Gy/min was employed in all the radiation groups, in which the administered dosages were 0, 0.25, 0.5, 1, 2, 3, 4, 5 and 6 Gy, respectively. Finally, the dose-effect relationship was analyzed by employing clone counting method, and the radiosensitization and synergistic effects of MK1775 on the three kinds of gene mutant cells were analyzed. Results： The different gene mutation types corresponded to different hyper-radiosensitivity doses. The numbers of PC9, A549 and H1299 cell clones were decreased to 56.4%, 54.5% and 73.2% respectively after adding MK1775 inhibitor, which indicated that the synergy effect exists indeed between MK1775 and radiation. The α/β values were negative in PC9 and H1299 cells （except of A549 cells） before MK1775 treatment, and all the α/β values in PC9, H1299 and A549 cells in MK1775 combined with radiation group were positive. So it was indicated that the radiosensitizing effect of MK1775 inhibitor only worked when α/β value was negative. Additionally, there was significant difference between the radiation alone group and MK1 775 combined with radiation group （P 〈 0.05）. Conclusion： The different driver genes correspond to different α and β values, thus correspond to different equivalent biological doses. Simultaneously, MK1775 maybe have the different radiosensitization or radiosynergistic effect for lung cancer cells with different driver genotypes.
作者
贺晓东
粟波
叶影
沈皓
HE Xiaodong1, SU Bo2, YE Ying1, SHEN Hao3(1. Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tong~i University School of Medicine, Shanghai 200433, China; 2. Clinical Support Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; 3. Institute of Modern Physics, Fudan University, Shanghai 200433, Chin)
出处
《肿瘤》
CAS
CSCD
北大核心
2018年第3期196-203,共8页
Tumor
