[Effect of licochalcone A on autophagy in renal cell carcinoma via PI3K/Akt/mTOR signaling pathway]

Zhongguo Zhong Yao Za Zhi. 2018 Sep;43(17):3545-3552. doi: 10.19540/j.cnki.cjcmm.20180427.001.
[Article in Chinese]

Abstract

To investigate the effect of licochalcone (LCA) on autophagy in renal cell carcinoma (RCC), and further determine whether the mechanism is correlated with the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of mTOR pathway, RCC 786-O and 769-P were used as study subjects. MTT assay was used to examine cell proliferation. The abilities of migration and invasion were detected by Transwell. The autophagy was observed under the fluorescence microscope through acridine orange staining. Green fluorescence spots were observed in Ad-GFP-LC3 transfection experiment. The protein expression was detected by Western blot. MTT assay results showed a dose and time-dependent cytotoxicity in the two cell lines treated with LCA. LCA inhibited migration and invasion in 786-O and 769-P cells. LCA increased the expression levels of LC3-Ⅱ, beclin 1, Atg5, and down-regulated the expression of p62. In addition, LCA inhibited the PI3K/Akt/mTOR pathway. Furthermore, the inhibition of PI3K/Akt by LY294002 or that of mTOR by rapamycin augmented LCA-induced autophagy. The findings demonstrated that LCA inhibited the proliferation, migration, invasion, and induced autophagy by inactivating PI3K/Akt/mTOR signaling pathway in 786-O and 769-P cells.

Keywords: PI3K/Akt/mTOR; autophagy; licochalcone A; renal cell carcinoma(RCC).

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy / drug effects*
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Chalcones / pharmacology*
  • Humans
  • Kidney Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Chalcones
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • licochalcone A