Down-Regulating Receptor Interacting Protein Kinase 1 (RIP1) Promotes Oxaliplatin-Induced Tca8113 Cell Apoptosis

Med Sci Monit. 2015 Oct 13:21:3089-94. doi: 10.12659/msm.894184.

Abstract

Background: Oxaliplatin is a crucial chemotherapy drug that plays an important role in colorectal cancer and oral cancer treatment. However, the molecular mechanism of oxaliplatin in killing tongue squamous cell cancer cells is still unknown. This paper investigates the mechanism of by which oxaliplatin regulates tongue squamous cell carcinoma Tca8113 cell survival and death.

Material and methods: Tca8113 was treated with 1 μmol/L oxaliplatin for 24 h. Tca8113 cell proliferation and apoptosis were determined by MTT method and flow cytometry, respectively. Western blot was applied to detect receptor-interacting protein kinase 1 (RIP1) level. Tca8113 was transfected with siRNA RIP1 and then treated with 1 μmol/L oxaliplatin, and the cell apoptosis was detected.

Results: We found that 1 μmol/L oxaliplatin could inhibit Tca8113 cell growth (cell survival rate was 19.3%), reduce mitochondrial membrane potential (reduce 82.3%) and phosphatidylserine eversion (positive rate was 62.7%), and activate caspase-3 (increased 2.6 times). We also found that 1 μmol/L oxaliplatin treatment could increase RIP1 expression in Tca8113 cells. Cell apoptosis rate increased after siRNA RIP1 and 1 μmol/L oxaliplatin treatment (apoptosis rate was 90.2%).

Conclusions: Down-regulating RIP1 promotes oxaliplatin induced Tca8113 cells apoptosis.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Apoptosis*
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3 / metabolism
  • Cell Line, Tumor / drug effects
  • Cell Proliferation
  • Cell Survival
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Membrane Potential, Mitochondrial
  • Membrane Potentials
  • Organoplatinum Compounds / chemistry*
  • Oxaliplatin
  • Phosphatidylserines / chemistry
  • RNA, Small Interfering / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics*
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Tongue Neoplasms / pathology
  • Transfection

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Phosphatidylserines
  • RNA, Small Interfering
  • Oxaliplatin
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • CASP3 protein, human
  • Caspase 3