Zheng Wubin, Sun Guoqiang, Li Zhitao, Wu Fan, Sun Guangshun, Cao Hongyong, Zhou Jin, Ma Yong
Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Front Surg. 2022 Apr 12;9:895982. doi: 10.3389/fsurg.2022.895982. eCollection 2022.
Protein tyrosine kinase (PTK) signaling pathway has been confirmed to be involved in the proliferation, differentiation and migration of tumor cells. Anlotinib, as a multi-target tyrosine kinase inhibitor, which can inhibit the expression of vascular endothelial growth factor receptor (VEGFR), has been confirmed to have significant therapeutic effects on non-small cell lung cancer, medullary thyroid carcinoma, and soft tissue sarcoma, but the therapeutic effect on gastric cancer (GC) is still unclear.
Anlotinib was screened out of 880 drugs through Cell Counting Kit 8 (CCK-8) technology. TCGA was used to detect the expression of VEGFR in GC, and Kaplan-Meier Plotter was used to analyze the correlation between the expression of VEGFR and the survival rate of GC patients. The impacts exerted by anlotinib to GC cell proliferating, migrating and invading processes were assessed through wound healing assay, transwell assay, and proliferation assay in vitro. In vivo experiments of GC were performed in C57/B6 mouse model to evaluate the function of anlotinib and PD-1 antibody.
It was found from more than compunds that anlotinib has a significant inhibitory effect on GC cells. In vitro experiments show that anlotinib can significantly inhibit the proliferation, invasion and proliferation of GC cells. The expression level of VEGFR is related to the prognosis and survival of GC. GC patients with low expression of VEGFR have better survival. Anlotinib can inhibit the expression of PD-L1, and achieve better therapeutic effects after combined with PD-1 antibody.
The present study reveals that anlotinib down regulates PD-L1. The combination of anlotinib and PD-1 monoclonal antibody is beneficial to GC therapy.
蛋白酪氨酸激酶（PTK）信号通路已被证实参与肿瘤细胞的增殖、分化和迁移。安罗替尼作为一种多靶点酪氨酸激酶抑制剂，可抑制血管内皮生长因子受体（VEGFR）的表达，已被证实在非小细胞肺癌、甲状腺髓样癌和软组织肉瘤中具有显著治疗效果，但对胃癌（GC）的治疗效果仍不明确。
通过细胞计数试剂盒8（CCK-8）技术从880种药物中筛选出安罗替尼。利用TCGA检测胃癌中VEGFR的表达，并使用Kaplan-Meier Plotter分析VEGFR表达与胃癌患者生存率之间的相关性。通过体外伤口愈合试验、Transwell试验和增殖试验评估安罗替尼对胃癌细胞增殖、迁移和侵袭过程的影响。在C57/B6小鼠模型中进行胃癌的体内实验，以评估安罗替尼和PD-1抗体的作用。
从多种化合物中发现安罗替尼对胃癌细胞具有显著抑制作用。体外实验表明，安罗替尼可显著抑制胃癌细胞的增殖、侵袭和迁移。VEGFR的表达水平与胃癌的预后和生存相关。VEGFR低表达的胃癌患者生存较好。安罗替尼可抑制PD-L1的表达，与PD-1抗体联合使用后可取得更好的治疗效果。
本研究揭示安罗替尼可下调PD-L1。安罗替尼与PD-1单克隆抗体联合使用有利于胃癌治疗。
