联合抑制低氧诱导因子1α与信号转导和转录活化因子3对人喉鳞状细胞癌裸鼠移植瘤放疗的影响

Effect of inhibiting of HIF-1α and STAT3 combined with irradiation on laryngeal squamous carcinoma cells of xenograft mice

目的探讨联合抑制低氧诱导因子1α(hypoxia-inducible factor 1α,HIF-1α)与信号转导和转录活化因子3(signal transducer and activatorof transcription3,STAT3)对裸鼠人喉鳞状细胞癌(简称鳞癌)移植瘤放疗增敏作用其机制。方法将制备的喉鳞癌移植瘤裸鼠随机分为空白对照组(A)、放疗组(B)、放疗联合AG490组(C)、放疗联合PX-478组(D)和放疗联合AG490加PX-478组(E)。测量并计算移植瘤体积的变化,应用免疫组织化学法检测Ki67和HIF-1α表达。应用Westernblot法检测PARP-1裂解片段表达。结果荷瘤小鼠肿瘤体积在E组与C组、D组相比均明显减小,差异具有极显著性(t=12.367、11.598,P均<0.01)。HIF-1α表达在E组与C组、D组相比明显减低((t=5.422、3.000,P均<0.05)。Ki67指数在E组与C组、D组比较统计学均有极显著性差异(t=4.479、4.352,P均<0.01)。PARP-1表达E组与C组、D组相比均明显增高(t=5.507、7.102,P均<0.05)。结论喉癌裸鼠移植瘤体内实验证明联合抑制STAT3和HIF-1α信号途径对放疗有明显增敏作用。

OBJECTIVE To investigate theradiosensitization of combined inhibition of signal transducer and activator of transcription 3（STAT3） and hypoxia-inducible factor-1α（HIF-1α）on laryngeal squamous carcinoma of xenograft mice and its underlying mechanisms. METHODS Xenograft mice were divided into 5 groups randomly： control group（A）, irradiation group（B）, irradiation and AG490 group（C）, irradiation and PX478 group（D）, irradiation combined AG490 and PX478 group（E）. The size of xenograft tumor was measured and calculated. The expression of Ki67 and HIF-1α was detected by immunohistochemical method. Western blot was used to detect the expression of PARP1. RESULTS The size of xenograft tumor in group E was smaller compared with that in group C and group D. There were significantly difference between them respectively （t=12.367, 11.598, P=0.000）. The expression of HIF-1α in group E was lower than that in group C and group D respectively, and there were significantly difference respectively （t=5.422, 3.000, P〈0.05）. Ki67 index in group E was lower compared with that in group C and group D respectively and there were significantly difference respectively （t=4.479, 4.352, P〈0.05）. The level of cleaved PARP-1 in group E was higher than that in group C and group D respectively and there were significantly difference respectively （t=5.507, 7.102, P〈0.05）. CONCLUSION Combined inhibition of STAT3 and HIF-1α can increase the radiosensitivity of human laryngeal squamous carcinoma in tile xenograft mice.