Fu Jijun, Zeng Wenjuan, Chen Minshan, Huang Lijuan, Li Songpei, Li Zhan, Pan Qianrong, Lv Sha, Yang Xiangyu, Wang Ying, Yi Mengmeng, Zhang Jianye, Lei Xueping
The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Road, Guangzhou, China.
Chem Biol Interact. 2022 Jul 1;361:109966. doi: 10.1016/j.cbi.2022.109966. Epub 2022 May 2.
Tumor angiogenesis inhibitors such as Bevacizumab, Ramucirumab and Endostar have been applied to the therapy of non-small cell lung carcinoma (NSCLC) patients, especially for lung adenocarcinoma (LUAD). However, several safe concerns such as neutropenia, febrile neutropenia and hypertension pulmonary hemorrhage limit their further development. And they often showed poor efficacy and serious side effect for lung squamous cell carcinoma (LUSC) patient. Thus, identification of effective and safe tumor angiogenesis inhibitor for NSCLC therapy is warranted. Apigenin is a bioflavonoid with potential anti-tumor effect and perfect safety, but its effect on tumor angiogenesis and underlying mechanism are still unclear. Herein, we found that apigenin not merely suppressed endothelial cells related motilities but also reduced pericyte coverage. Further research showed that apigenin had strong suppressive activity against HIF-1α expression and its downstream VEGF-A/VEGFR2 and PDGF-BB/PDGFβR signaling pathway. Apigenin also reduced microvessel density and pericyte coverage on the xengraft model of NCI-H1299 cells, leading to suppression of tumor growth. Moreover, apigenein showed perfect anti-angiogenic effect in xengraft model of LUSC cell NCI-H1703 cells, indicating it may be developed into a potential angiogenesis inhibitor for LUSC patient. Collectively, our study provides new insights into the anti-tumor mechanism of apigenin and suggests that apigenin is a safe and effective angiogenesis inhibitor for NSCLC therapy.
贝伐单抗、雷莫西尤单抗和恩度等肿瘤血管生成抑制剂已应用于非小细胞肺癌（NSCLC）患者的治疗，尤其是肺腺癌（LUAD）。然而，诸如中性粒细胞减少、发热性中性粒细胞减少和高血压性肺出血等安全问题限制了它们的进一步发展。而且，它们对肺鳞状细胞癌（LUSC）患者往往疗效不佳且副作用严重。因此，有必要鉴定出用于NSCLC治疗的有效且安全的肿瘤血管生成抑制剂。芹菜素是一种具有潜在抗肿瘤作用且安全性良好的生物类黄酮，但其对肿瘤血管生成的作用及其潜在机制仍不清楚。在此，我们发现芹菜素不仅抑制内皮细胞相关的运动能力，还减少周细胞覆盖。进一步研究表明，芹菜素对HIF-1α表达及其下游的VEGF-A/VEGFR2和PDGF-BB/PDGFβR信号通路具有强烈的抑制活性。芹菜素还降低了NCI-H1299细胞异种移植模型中的微血管密度和周细胞覆盖，从而抑制肿瘤生长。此外，芹菜素在LUSC细胞NCI-H1703细胞的异种移植模型中显示出良好的抗血管生成作用，表明它可能被开发成为LUSC患者潜在的血管生成抑制剂。总的来说，我们的研究为芹菜素的抗肿瘤机制提供了新的见解，并表明芹菜素是用于NSCLC治疗的一种安全有效的血管生成抑制剂。
