title: [Autophagy inhibitor 3-methyladenine enhances the sensitivity of nasopharyngeal carcinoma cells to chemotherapy and radiotherapy].
abstract: OBJECTIVE
  To explore the effects of 3-methyladenine (3-MA, an autophagy inhibitor) on sensitivities of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy and the underlying mechanisms.
  
  
  METHODS
  Cell proliferation was examined by MTT and colony formation assay, while cell apoptosis was evaluated by annexin V/PI double staining and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining. Mitochondrial membrane potential was measured by commercial kit (JC-1). The expression of endoplasmic reticulum stress (ERS)-related protein, glucose-regulated protein 78 (GRP78) and autophagy-related protein beclin1, microtubule-associated protein 1 light chain 3 (LC3) were examined by Western blot.
  
  
  RESULTS
  Cisplatin (DDP), ionizing radiation (IR) or tunicamycin (TM) treatment obviously inhibited the proliferation of HONE-1 cells in a concentration-dependent and time-dependent manner. Compared with control group, pretreatment with 1 mmol/L of 3-MA significantly  reduced cell viability and enhanced the apoptosis in the DDP (6.00 μmol/L), 4.00 Gy IR or TM (1.00 μmol/L) groups. There was no significant difference in the apoptosis between the DDP (5.8%) and 4Gy IR (6.7%) groups. Compared with the control group, protein levels of GRP78, beclin1 and lipid-conjugated membrane-bound form (LC3-II) were significantly increased after the treatment of DDP, 4.00 Gy IR or TM, which were inhibited by pretreatment of 3-MA.
  
  
  CONCLUSIONS
  3-MA can sensitize HONE-1 cells to chemotherapy and radiotherapy, which is related to prevention of endoplasmic reticulum stress-induced autophagy in nasopharyngeal carcinoma cells.
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004, China.
authors.forename: Lele
authors.initials: L
authors.lastname: Song
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu Anhui 233030, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004, China.
authors.forename: Gende
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu Anhui 233030, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Priority Research Center for Cancer Research, University of Newcastle, Callaghan New South Wales 2308, Australia.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu Anhui 233030, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D002277:Carcinoma; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011838:Radiation-Sensitizing Agents; D014415:Tunicamycin; C025946:3-methyladenine; D000225:Adenine; D002945:Cisplatin