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

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.

• Authors: Ben Ma, Li-zhong Liang, Gui-qing Liao, Yu-jie Liang, Hai-chao Liu, Guang-sen Zheng, Yu-xiong Su
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 42 Issue 10 Pg. 774-80 (Nov 2013) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 23590333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• 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

Topics

• Adenine (analogs & derivatives, pharmacology)
• Antineoplastic Agents (therapeutic use)
• Apoptosis Regulatory Proteins (pharmacology)
• Autophagy (drug effects)
• Beclin-1
• Carcinoma, Adenoid Cystic (drug therapy, 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, pathology)
• Tetrazolium Salts
• Thiazoles