Angiotensin-(1-7) can promote cell migration and tumor growth of clear cell renal cell carcinoma

J Physiol Pharmacol. 2022 Dec;73(6). doi: 10.26402/jpp.2022.6.04. Epub 2023 Apr 17.

Abstract

Renal cell carcinoma (RCC) is the most common kidney malignancy, accounting for 3% of all cancers. Despite significant advances in targeted therapies and immunotherapy, many patients with RCC develop resistance to available drugs. Angiotensin-(1-7) (Ang-(1-7)) is a heptapeptide and a member of the renin-angiotensin system which regulates the cardiovascular and the renal system. It has been proposed as a potential anticancer agent for the treatment of various types of cancers, but data regarding its efficiency against RCC are conflicting. The aim of our study was to evaluate the effects of Ang-(1-7) in RCC models in vitro and in vivo. We performed a series of in vitro experiments investigating the effects of Ang-(1-7) on cell viability and migration in Caki-1 and Caki-2 cell lines. In addition, we carried out an in vivo study in xenografts of Caki-1 cells in nude mice. In results: Ang-(1-7) or A779, an antagonist of its receptor MasR (Mas receptor), showed no effect on cell viability. Ang-(1-7) promoted cell migration in a dose-dependent manner by inducing the activation of MasR. It also promoted tumor growth in vivo, and this effect was not inhibited by the blockade of MasR. No effects on cell proliferation or tumor vessel density were observed. The results suggest that Ang-(1-7) can exert protumorigenic activity in RCC, however, further research on other RCC models is needed to better recapitulate the heterogeneity of the disease.

MeSH terms

  • Angiotensin I / metabolism
  • Angiotensin I / pharmacology
  • Animals
  • Carcinoma, Renal Cell* / drug therapy
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Mice
  • Mice, Nude
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Proto-Oncogene Mas

Substances

  • Proto-Oncogene Mas
  • angiotensin I (1-7)
  • Peptide Fragments
  • Angiotensin I