Neoplasma Vol.68, No.4, p.770–779, 2021
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| Title: The role of angiotensin-(1-7) on acquired platinum resistance-induced angiogenesis in non-small cell lung cancer in vitro and in vivo |
| Author: Yan-Lai Geng, Yong-Jie Ding, Lei Ni, Kan-Di Xu, Van-Minh Le, Ri Ji, Yun Feng |
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Abstract: 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.
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| Keywords: NSCLC; Ang-(1-7); acquired platinum resistance; tumor-associated angiogenesis; ACE2/Ang-(1-7)/Mas axis |
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Published online: 26-May-2021
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| Year: 2021, Volume: 68, Issue: 4 |
Page From: 770, Page To: 779 |
doi:10.4149/neo_2021_201213N1347
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