Down-regulation of FRα inhibits proliferation and promotes apoptosis of cervical cancer cells in vitro

Asian Pac J Cancer Prev. 2014;15(14):5667-72. doi: 10.7314/apjcp.2014.15.14.5667.

Abstract

Folate receptor alpha (FRα) mediates folate uptake by endocytosis, and while folate is essential to DNA methylation and synthesis and may have an important role in proliferating cells. FRα is known to be expressed in rapidly proliferating cells, including many cancer cell lines, but there has been no systematic assessment of expression in cervical cancer cell lines. The aim of the present study was to evaluate the effects of FRα on proliferation and apoptosis of cervical cells and correlation mechanism. In this study, we investigated the biological function of FRα in Hela cells using RNA interference. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK8) assay, while cell cycling and apoptosis were assessed by flow cytometry, mRNA levels by real time- PCR and protein levels of FRα, c-Fos and c-Jun by Western blotting. The results revealed that FRα was highly expressed in Hela cells and its silencing with a small interfering RNA (siRNA) inhibited cell proliferation and induced cell apoptosis, arresting the cell cycle in G0/G1 stages while decreasing the proportion in S and G2/M stages, and suppressed the expression levels of c-Fos and c-Jun. In conclusion, the results of this study indicated that FRα down-regulation might be capable of suppressing cervical cancer cell proliferation and promoting apoptosis. It suggested that FRα might be a novel therapeutic target for cervical cancer.

MeSH terms

  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Down-Regulation
  • Endocytosis
  • Female
  • Folate Receptor 1 / biosynthesis
  • Folate Receptor 1 / genetics*
  • Folic Acid / metabolism
  • G1 Phase Cell Cycle Checkpoints / genetics
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / biosynthesis
  • M Phase Cell Cycle Checkpoints / genetics
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • RNA Interference
  • RNA, Messenger
  • RNA, Small Interfering
  • S Phase Cell Cycle Checkpoints
  • Uterine Cervical Neoplasms / genetics*

Substances

  • Folate Receptor 1
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • RNA, Small Interfering
  • Folic Acid
  • JNK Mitogen-Activated Protein Kinases