The Effect of PTCH1 on Ovarian Cancer Cell Proliferation and Apoptosis

Cancer Biother Radiopharm. 2019 Mar;34(2):103-109. doi: 10.1089/cbr.2018.2626. Epub 2018 Dec 6.

Abstract

Objective: Patched (PTCH1) is an important receptor protein in the Hedgehog pathway and plays a tumor suppressor role in a variety of tumors. This study was to detect the expression of PTCH1 in ovarian cancer (OC) tissues to analyze the relationship between expression of PTCH1 and prognosis, and to explore its role in regulating OC cell proliferation and apoptosis.

Materials and methods: OC tissues and normal ovarian tissues were collected to detect PTCH1 expression. SKOV3, A2780, Caov3, and IOSE80 cells were cultured in vitro to test PTCH1 expression. pIRES2-Scramble and pIRES2-PTCH1 were transfected into SKOV3 and A2780 cells, respectively. PTCH1 and Gli1 expressions were detected by western blot. Cell apoptosis was determined by flow cytometry. Cell proliferation was assessed by EdU staining.

Results: PTCH1 expression was significantly decreased in OC tissue compared with normal ovarian tissue and was associated with tumor size, TNM stage, and pathological grade (p < 0.05). The prognosis of patients with low PTCH1 expression was obviously worse than that of patients with high PTCH1 expression. The expression of PTCH1 in OC SKOV3, A2780, and Caov3 cells was markedly lower than that in normal ovarian epithelial IOSE80 cells. Transfection of pIRES2-PTCH1 apparently upregulated PTCH1 level, inhibited GLI1 expression and cell proliferation, and promoted apoptosis of SKOV3 and A2780 cells.

Conclusion: PTCH1 level in OC was abnormally decreased and related to prognosis. Overexpression of PTCH1 inhibited GLI1 expression, attenuated OC cell proliferation, and induced apoptosis, suggesting that manipulation of PTCH1 expression might be a novel approach for the treatment of OC.

Keywords: Hedgehog; PTCH1; apoptosis; ovarian cancer; proliferation.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Female
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Patched-1 Receptor / biosynthesis*
  • Patched-1 Receptor / genetics
  • Prognosis
  • Transfection
  • Zinc Finger Protein GLI1 / biosynthesis

Substances

  • GLI1 protein, human
  • PTCH1 protein, human
  • Patched-1 Receptor
  • Zinc Finger Protein GLI1