Gu Zhenlin, Zhu Weiguo, Wang Wanwei, Xu Yingying, Jiang Lei, Huang Jiasheng, Huang Jing
Department of Vascular Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China.
Department of Radiation Oncology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China.
J Oncol. 2022 Aug 31;2022:5632744. doi: 10.1155/2022/5632744. eCollection 2022.
Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and has antitumor activity in a variety of solid tumors. Given that, our study was designed to unearth the mechanism of anlotinib in radioresistant esophageal cancer (EC) cells.
Radioresistant EC cell lines TE-1R and KYSE-150R were established by multiple fractionated irradiation. Detection of cell proliferation was governed by the MTT assay, angiogenesis by the tube formation assay, and cell migration and invasion by the transwell assay. Lastly, RT-qPCR Western blotting was employed to detect the expression of related genes. Cancerous cells showing tumor growth were then detected by tumor xenografts in mice.
Radioresistant EC cell lines TE-1R and KYSE-150R were successfully established. Anlotinib downregulated EphA2 inhibited proliferation, angiogenesis, migration, and invasion of radioresistant EC cells . The up-regulated expression of EphA2 in both EC cell lines and radioresistant EC cells, along with anlotinib, in turn, inhibited the expression of EphA2 in radioresistant EC cells. Inhibiting EphA2 also enhanced anlotinib-mediated effects on radioresistant EC cells, so as to restrain cell proliferation, angiogenesis, migration, and invasion. Correspondingly, overexpression of EphA2 is capable of reversing the therapeutic effect of anlotinib on radioresistant EC cells. Also, anlotinib enhances the inhibitory effect of irradiation on mice.
It is concluded that anlotinib inhibits EphA2 expression, thereby suppressing angiogenesis and resensitizing EC cells to radiotherapy, providing another perspective to overcome radioresistance in EC.
安罗替尼是一种新型的多靶点酪氨酸激酶抑制剂，可抑制肿瘤血管生成，对多种实体瘤具有抗肿瘤活性。鉴于此，我们开展本研究以探究安罗替尼在耐放射性食管癌（EC）细胞中的作用机制。
通过多次分割照射建立耐放射性EC细胞系TE-1R和KYSE-150R。采用MTT法检测细胞增殖，采用管腔形成试验检测血管生成，采用Transwell试验检测细胞迁移和侵袭。最后，运用RT-qPCR和蛋白质印迹法检测相关基因的表达。然后通过小鼠肿瘤异种移植检测显示肿瘤生长的癌细胞。
成功建立了耐放射性EC细胞系TE-1R和KYSE-150R。安罗替尼下调EphA2的表达，抑制耐放射性EC细胞的增殖、血管生成、迁移和侵袭。在EC细胞系和耐放射性EC细胞中EphA2的表达上调，而安罗替尼反过来抑制耐放射性EC细胞中EphA2的表达。抑制EphA2也增强了安罗替尼对耐放射性EC细胞的作用，从而抑制细胞增殖、血管生成、迁移和侵袭。相应地，EphA2的过表达能够逆转安罗替尼对耐放射性EC细胞的治疗效果。此外，安罗替尼增强了辐射对小鼠的抑制作用。
得出结论，安罗替尼抑制EphA2表达，从而抑制血管生成并使EC细胞对放疗重新敏感，为克服EC中的放射抗性提供了另一个视角。
