CAJ | 학술논문

目的探讨血管内皮抑素对肺鳞癌细胞系H-520细胞放射增敏作用的机制.方法重组人血管内皮抑素联合60 Co γ线作用于H-520细胞后,集落形成实验检测重组人血管内皮抑素对H-520细胞的放射增敏作用;流式细胞术检测细胞周期变化及磷酸化p38-MAPK蛋白的表达水平;RT-PCR检测周期相关基因cyclin D1、cdk2、cdk4及凋亡相关基因survivin的表达情况;Western-blotting检测磷酸化Akt蛋白表达情况.结果血管内皮抑素可以增加细胞对60 coγ射线的放射敏感性,联合组D0、Dq、N、D10、SF2较照射组低,放射增敏比为1.45;200μg/ml血管内皮抑素处理后H-520细胞发生G0/G1期阻滞,周期相关基因cyclin D1、cdk2、cdk4及凋亡相关基因survivin表达下降;血管内皮抑素联合照射后磷酸化p38-MAPK蛋白及磷酸化Akt蛋白表达下降.结论血管内皮抑素可能通过抑制H-520细胞增殖,诱导细胞发生G0/G1期阻滞,促进细胞凋亡及阻断p38-MAPK 和P13K/Akt信号通路传导,发挥放射增敏作用.
목적 탐토혈관내피억소대폐린암세포계H-520세포방사증민작용적궤제.방법 중조인혈관내피억소연합60 Co γ선작용우H-520세포후,집락형성실험검측중조인혈관내피억소대H-520세포적방사증민작용;류식세포술검측세포주기변화급린산화p38-MAPK단백적표체수평;RT-PCR검측주기상관기인cyclin D1、cdk2、cdk4급조망상관기인survivin적표체정황;Western-blotting검측린산화Akt단백표체정황.결과 혈관내피억소가이증가세포대60 coγ사선적방사민감성,연합조D0、Dq、N、D10、SF2교조사조저,방사증민비위1.45;200μg/ml혈관내피억소처리후H-520세포발생G0/G1기조체,주기상관기인cyclin D1、cdk2、cdk4급조망상관기인survivin표체하강;혈관내피억소연합조사후린산화p38-MAPK단백급린산화Akt단백표체하강.결론 혈관내피억소가능통과억제H-520세포증식,유도세포발생G0/G1기조체,촉진세포조망급조단p38-MAPK 화P13K/Akt신호통로전도,발휘방사증민작용.
Objective To investigate the mechanism of radiosensitizing effects of endostatin on H-520 human lung squamous cancer cells.Methods H-520 cells was treated with endostatin and/or radiation.Colony-forming assays were used to indicate the radiosensitising effects.Cell cycle distribution and expression of phosphor-p38-MAPK were assayed by FCM,and cyclin D1,cdk2,cdk4 and survivin mRNA leveh were assayed by RT-PCR.Phosphor-Akt was evaluated by Western-blotting.Results Combination of endostatin and irradiation inhibited the proliferation of H-520 cells.According to the colony-forming assays,the D0,Dq,D10 and SF2 values of the combination groups were much lower than those of irradiation groups.The sensitization enhancement ratio(SER)was 1.51.G2/M arrest occurred after 4 Gy irradiation.The gene expression of cyclin D1,cdk2,ckd4 and survivin and phosphor-Akt protein were down-regulated after treatment.The expression of phosphor-p38-MAPK protein was also down-regulated after treatment with 200 μg/ml endostar.Conclusions Endostatin inhibits the growth of H-520 cells and radiosensitizes the cells by induction of G0/G1 arrest,cell apoptosis and down-regulation of gene expression of cyelin D1,cdk2,cdk4 and reduces the phosphorylation of Akt and p38-MAPK.