Renin-angiotensin system (RAS) signaling has been implicated in the development of cancer. The new RAS ACE2/Ang-(1-7)/Mas axis antagonizes the classical ACE/Ang II/AT1R axis. Ang-(1-7) has pleiotropic roles in lung cancer including suppressing proliferation, angiogenesis, and metastasis. This research was designed to investigate the effect of Ang-(1-7) on tumor-associated angiogenesis in DDP-resistant lung cancer cell lines. We first established acquired DDP-resistant cell lines A549 (A549-DDP) and LCC (LLC-DDP). We next performed RT-qPCR, western blot, ELISA, tube formation, microvessel density detection, immunohistochemistry, and tumor formation assays. The results showed that the mRNA and protein levels of RAS components and vascular endothelial growth factor A (VEGFa) were lessened in the A549/LLC-DDP-Ang-(1-7) group compared with the A549/LLC-DDP group. This effect could be blocked by the MAS receptor antagonist A779. The data revealed that Ang-(1-7) could perform its antiangiogenic function by PI3K/AKT and MAPK pathways. Furthermore, the impact of Ang-(1-7) on tumor-associated angiogenesis has been confirmed in lung cancer xenograft model with acquired DDP resistance. These results provide a theoretical basis for designing therapeutic strategies for targeting Ang-(1-7) in the treatment of NSCLC.

中文翻译：

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血管紧张素-(1-7) 在体外和体内对非小细胞肺癌中获得性铂耐药性诱导的血管生成的作用。

肾素-血管紧张素系统 (RAS) 信号传导与癌症的发展有关。新的 RAS ACE2/Ang-(1-7)/Mas 轴对抗经典的 ACE/Ang II/AT1R 轴。Ang-(1-7) 在肺癌中具有多种作用，包括抑制增殖、血管生成和转移。本研究旨在研究 Ang-(1-7) 对 DDP 抗性肺癌细胞系中肿瘤相关血管生成的影响。我们首先建立了获得性 DDP 抗性细胞系 A549（A549-DDP）和 LCC（LLC-DDP）。我们接下来进行了 RT-qPCR、蛋白质印迹、ELISA、管形成、微血管密度检测、免疫组织化学和肿瘤形成分析。结果显示，与A549/LLC-DDP组相比，A549/LLC-DDP-Ang-(1-7)组RAS组分和血管内皮生长因子A(VEGFa)的mRNA和蛋白水平降低。这种作用可以被 MAS 受体拮抗剂 A779 阻断。数据显示，Ang-(1-7) 可以通过 PI3K/AKT 和 MAPK 途径发挥其抗血管生成功能。此外，Ang-(1-7) 对肿瘤相关血管生成的影响已在具有获得性 DDP 抗性的肺癌异种移植模型中得到证实。这些结果为设计靶向Ang-(1-7)治疗NSCLC的治疗策略提供了理论基础。Ang-(1-7) 对肿瘤相关血管生成的影响已在具有获得性 DDP 抗性的肺癌异种移植模型中得到证实。这些结果为设计靶向Ang-(1-7)治疗NSCLC的治疗策略提供了理论基础。Ang-(1-7) 对肿瘤相关血管生成的影响已在具有获得性 DDP 抗性的肺癌异种移植模型中得到证实。这些结果为设计靶向Ang-(1-7)治疗NSCLC的治疗策略提供了理论基础。