Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands

J Oral Pathol Med. 2013 Nov;42(10):774-80. doi: 10.1111/jop.12066. Epub 2013 Apr 17.

Abstract

Background: The relationship between autophagy and chemotherapy in cancer has been studied a lot recent years. However, there is currently no study on the role of autophagy in chemotherapy of adenoid cystic carcinoma (ACC) of human salivary glands. We hypothesized that autophagy plays a protective role for human salivary gland ACC cells during chemotherapy, diminishes the effect of treatment, and ultimately results in poor sensitivity to chemotherapy.

Materials and methods: After inhibition of autophagy by 5 mM 3-methyladenine (3MA), 20 μM Chloroquine (CQ), or Beclin-1 shRNA, we examined the sensitivity of human salivary gland ACC cells to different concentrations of cis-diamminedichloroplatinum (CDDP) using MTT assay. Also, levels of autophagy in ACC cells treated by CDDP were assessed by western blot, GFP-LC3 fluorescence and transmission electron microscopy (TEM).

Results: Inhibition of autophagy induced by 3MA, CQ, or Beclin-1 shRNA could all enhance human salivary gland ACC cell death treated by CDDP. And, levels of autophagy in these cells showed a significant increase after treated by CDDP.

Conclusion: Autophagy played a protective role for human salivary gland ACC cells during CDDP chemotherapy. Inhibition of autophagy in these cells could enhance cisplatin cytotoxicity-effects. These findings indicate a novel and promising way to reduce chemotherapy resistance and improve treatment outcome in human salivary gland ACC.

Keywords: adenoid cystic carcinoma; autophagy; chemotherapy; cisplatin; head and neck cancer; salivary gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis Regulatory Proteins / pharmacology
  • Autophagy / drug effects*
  • Beclin-1
  • Carcinoma, Adenoid Cystic / drug therapy*
  • Carcinoma, Adenoid Cystic / pathology
  • Cell Culture Techniques
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chloroquine / pharmacology
  • Cisplatin / therapeutic use*
  • Coloring Agents
  • Drug Resistance, Neoplasm / drug effects*
  • Green Fluorescent Proteins
  • Humans
  • Luminescent Agents
  • Membrane Proteins / pharmacology
  • Microtubule-Associated Proteins / analysis
  • Salivary Gland Neoplasms / drug therapy*
  • Salivary Gland Neoplasms / pathology
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Coloring Agents
  • Luminescent Agents
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Tetrazolium Salts
  • Thiazoles
  • Green Fluorescent Proteins
  • 3-methyladenine
  • Chloroquine
  • thiazolyl blue
  • Adenine
  • Cisplatin