title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Ma
authors.forename: Li-zhong
authors.initials: LZ
authors.lastname: Liang
authors.forename: Gui-qing
authors.initials: GQ
authors.lastname: Liao
authors.forename: Yu-jie
authors.initials: YJ
authors.lastname: Liang
authors.forename: Hai-chao
authors.initials: HC
authors.lastname: Liu
authors.forename: Guang-sen
authors.initials: GS
authors.lastname: Zheng
authors.forename: Yu-xiong
authors.initials: YX
authors.lastname: Su
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000473:pathology; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D002945:Cisplatin / Q000627:therapeutic use*; D004396:Coloring Agents; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D049452:Green Fluorescent Proteins; D006801:Humans; D049408:Luminescent Agents; D008565:Membrane Proteins / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000032:analysis; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D004396:Coloring Agents; D049408:Luminescent Agents; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D049452:Green Fluorescent Proteins; C025946:3-methyladenine; D002738:Chloroquine; C022616:thiazolyl blue; D000225:Adenine; D002945:Cisplatin
keywords: adenoid cystic carcinoma; autophagy; chemotherapy; cisplatin; head and neck cancer; salivary gland