Qi Xuejiao, Zhao Yinlong, Yang Song, Sun YuMeng, Liu Honglei, Liu Pengyu, Feng Shiyao, Tui Hongbo, Yuan Zheng, Yang Jiankai, Bu Hui
Department of Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China.
Department of Intensive Care Unit, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China.
Anticancer Agents Med Chem. 2023;23(6):709-716. doi: 10.2174/1871520622666220827125929.
The blockade of programmed cell death-1 (PD-1) and recombinant human endostatin can be used for the treatment of non-small cell lung cancer (NSCLC) and its metastasis. This study aims to explore the therapeutically potential of PD-1 blockade plus Endostar in brain metastasis of NSCLC.
The mouse brain metastases model was established using Lewis lung carcinoma luciferase (LLC-Luc) and PC-9-Luc cells. Tumor metastasis in the brain and tumor burden were analyzed by using bioluminescence imaging (BLI), qRT-PCR and ELISA which were used to determine the mRNA and protein levels of biomarkers in tumor tissues. Immunohistochemical staining was used to determine the expression and location of CD31 in tumor tissues in the brain.
Treatment with anti-PD-1 and Endostar suppressed tumor metastasis in the brain and prolonged overall survival rate in LLC-Luc and PC-9-Luc brain metastases mouse model. In addition, treatment with anti-PD-1 and Endostar inhibited the expressions of CD31 and VEGF in tumor tissues in the brain. Furthermore, treatment with anti-PD- 1 and Endostar significantly suppressed the levels of IL1β, IFNγ, and TGFβ in the tumor tissues.
The combination of PD-1 blockade and endostar suppressed brain metastases of NSCLC.
程序性细胞死亡蛋白1（PD-1）阻断剂和重组人内皮抑素可用于治疗非小细胞肺癌（NSCLC）及其转移。本研究旨在探讨PD-1阻断剂联合恩度治疗NSCLC脑转移的潜在疗效。
利用Lewis肺癌荧光素酶（LLC-Luc）和PC-9-Luc细胞建立小鼠脑转移模型。采用生物发光成像（BLI）、qRT-PCR和ELISA分析脑内肿瘤转移和肿瘤负荷，这些方法用于测定肿瘤组织中生物标志物的mRNA和蛋白水平。免疫组织化学染色用于确定脑内肿瘤组织中CD31的表达和定位。
抗PD-1和恩度治疗可抑制LLC-Luc和PC-9-Luc脑转移小鼠模型的脑内肿瘤转移，延长总生存率。此外，抗PD-1和恩度治疗可抑制脑内肿瘤组织中CD31和VEGF的表达。此外，抗PD-1和恩度治疗可显著抑制肿瘤组织中IL1β、IFNγ和TGFβ的水平。
PD-1阻断剂与恩度联合应用可抑制NSCLC脑转移。
