title: Endoplasmic reticulum stress-induced autophagy determines the susceptibility of melanoma cells to dabrafenib.
abstract: Melanoma is one of the deadliest skin cancers and accounts for most skin-related deaths due to strong resistance to chemotherapy drugs. In the present study, we investigated the mechanisms of dabrafenib-induced drug resistance in human melanoma cell lines A375 and MEL624. Our studies support that both endoplasmic reticulum (ER) stress and autophagy were induced in the melanoma cells after the treatment with dabrafenib. In addition, ER stress-induced autophagy protects melanoma cells from the toxicity of dabrafenib. Moreover, inhibition of both ER stress and autophagy promote the sensitivity of melanoma cells to dabrafenib. Taken together, the data suggest that ER stress-induced autophagy determines the sensitivity of melanoma cells to dabrafenib. These results provide us with promising evidence that the inhibition of autophagy and ER stress could serve a therapeutic effect for the conventional dabrafenib chemotherapy.
authors.affiliation: Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University; Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University; Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Ziping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University; Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University; Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Kunli
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University; Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University; Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University; Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Huang
authors.affiliation: Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Gong
authors.affiliation: Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University; Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D010091:Oximes / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; C561627:dabrafenib
keywords: ER stress; apoptosis; autophagy; dabrafenib; melanoma