title: Inhibition of autophagy augments chemotherapy in human salivary adenoid cystic carcinoma.
abstract: Although cisplatin (DDP)-based adjuvant chemotherapy is widely used in the treatment of salivary adenoid cystic carcinoma (SACC), SACCs have developed resistance to cisplatin, resulting in chemotherapy failure. Autophagy serves as a critical adaptive response, which was increased in tumor cells in chemotherapy. However, the function of autophagy is not clear in SACC. In this study, apoptosis induced by DDP in SACC high metastatic cell line (ACC-M) was revealed using MTT assay, flow cytometry, and caspase-3 immunoblotting. The autophagy activation induced by DDP treatment was measured by transmission electron microscopy, green fluorescent protein-light chain 3 plasmid transfection LC3 immunoblotting and p62 immunoblotting. 3-methyladenine (3-MA) or small interference RNA targeting beclin 1 (beclin 1 siRNA) inhibited autophagy and significantly enhanced DDP-induced apoptosis. ACC-M xenografts in nude mice further verified the synergistic effect of DDP and 3-MA. In conclusion, autophagy activation was caused to protect cancer cells from DDP-induced apoptosis and autophagy inhibition could be a promising strategy for adjuvant chemotherapy in SACC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Licheng
authors.initials: L
authors.lastname: Jiang
authors.forename: Shengyun
authors.initials: S
authors.lastname: Huang
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Keyi
authors.initials: K
authors.lastname: Li
authors.forename: Wengang
authors.initials: W
authors.lastname: Li
authors.forename: Shizhou
authors.initials: S
authors.lastname: Zhang
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.forename: Peihui
authors.initials: P
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000032:analysis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000071456:Sequestosome-1 Protein; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C025946:3-methyladenine; C505407:CASP3 protein, human; D053148:Caspase 3; D000225:Adenine; D002945:Cisplatin
keywords: DDP; adenoid cystic carcinoma; apoptosis; autophagy