ALA-PDT suppressed the cell growth by Akt-/Erk-mTOR-p70 s6k pathway in human SZ95 sebocytes in vitro

Photodiagnosis Photodyn Ther. 2018 Dec:24:1-6. doi: 10.1016/j.pdpdt.2018.06.024. Epub 2018 Jun 28.

Abstract

Background: Topical 5-aminolevulinic acid mediated photodynamic therapy (PDT) is known to be an effective method in treating acne vulgaris and other sebaceous gland-related diseases. The therapeutic mechanisms of ALA-PDT still remain undetermined. Our team has reported that ALA-PDT suppressed the cell growth in SZ95 sebocytes by mTOR-p70 S6K signaling. In this study, we aimed to investigate upstream of the mammalian target of rapamycin (mTOR) signaling cascade after ALA-PDT on cell growth of human SZ95 sebocytes.

Material and methods: Human SZ95 sebocytes were treated with different concentration of 5-ALA PDT. Western blotting was used to detect and analyze the protein expression level of P-Akt (T308)/Akt, P-Akt (S473)/Akt, P-Erk/Erk, P-AMPKα (T172)/AMPK, P-AMPKα1 (S485)/AMPKα2 (S491)/AMPK, P-PRAS40/PRAS40, RagC. Meanwhile, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences of P-p70 S6K/p70 S6K after ALA-PDT.

Results: mTOR pathway inhibitor rapamycin decreased the level of P-p70 S6K reduced by ALA-PDT. Conversely, mTOR pathway activator IGF-1. ALA-PDT reduced the level of P-Akt (T308), P-Erk, P-AMPKα (T172), P-AMPKα1 (S485)/AMPKα2 (S491) and P-PRAS40, and no change was observed in the level of Rag C.

Conclusion: ALA-PDT suppresses the cell growth in SZ95 cells through Akt-/Erk- mTOR -p70 s6k pathway rather than PRAS40-/RagC- mTOR pathway.

Keywords: ALA-PDT; SZ95; mTOR.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Aminolevulinic Acid / pharmacology*
  • Cell Enlargement / drug effects
  • Cell Line
  • DNA-Binding Proteins
  • Dose-Response Relationship, Drug
  • Humans
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacology*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Sebaceous Glands / cytology*
  • Sebaceous Glands / drug effects*
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • DNA-Binding Proteins
  • Photosensitizing Agents
  • Aminolevulinic Acid
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • Sirolimus