The TLR3, PI3K, survivin, FasL, and Fas genes as major risk factors of occurrence and development of cervical cancer disease

Gene. 2014 Oct 15;550(1):27-32. doi: 10.1016/j.gene.2014.08.009. Epub 2014 Aug 5.

Abstract

To investigate the role of TLR3/PI3K signals in the occurrence and development of cervical cancer disease, TLR3-siRNA was used to block key signaling pathways involved in cervical cancer metastasis that are pivotal to metastatic tumor cells but not to normal cells under ordinary physiologic conditions. Results show that tumor U14 cell growth, migration and invasion in TLR3-siRNA treatment group were significantly decreased. Through LY294002 suppressing targeted gene, the LY294002 treatment specifically and significantly knocked down the expressions of tumor TLR3 and PI3K proteins in cervical cancer mice. Furthermore, expressions of tumor Survivin and FasL proteins were markedly suppressed, whereas expressions of Fas protein were upregulated in LY294002 treatment group mice. LY294002 treatment suppressed tumor growth and increased the thymus and spleen indeces and survival days of cervical cancer mice. This study demonstrates that TLR3-siRNA and LY294002 treatments can markedly suppress cervical cancer cell invasion and tumor growth and increase survival life by silencing targeted genes.

Keywords: Cervical cancer; Mice; Survivin; TLR3/PI3K signals.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Morpholines / pharmacology
  • Organ Size / drug effects
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA Interference
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Spleen / drug effects
  • Spleen / pathology
  • Survivin
  • Thymus Gland / drug effects
  • Thymus Gland / pathology
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism*
  • Tumor Burden / drug effects
  • Tumor Burden / genetics
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / prevention & control
  • fas Receptor

Substances

  • Birc5 protein, mouse
  • Chromones
  • Enzyme Inhibitors
  • Fas Ligand Protein
  • Fas protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Repressor Proteins
  • Survivin
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • fas Receptor
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one