title: EphB4 inhibitor overcome the acquired resistance to cisplatin in melanomas xenograft model.
abstract: The purpose of this paper is to investigate the possible mechanisms of resistance to chemotherapy in melanoma from the perspective of molecular biology and to discuss the strategies to overcome them. Cisplatin, a DNA-damaging compound that triggers apoptotic cell death, is commonly used in the treatment of malignant melanoma. However, most patients develop mechanisms of acquired resistance and about 25% of them do not achieve tumor regression at all, due to intrinsic resistance to therapy. In the current study, we reported the tumor xenografts of the human A375 melanoma, after 40-weeks' consecutive therapy with cisplatin that developed resistance as a result of EphB4 overexpression. Moreover, the expression of phospho-AKT and phospho-ERK were significantly increased in cisplatin-resistant tumors. In addition, combined of cisplatin with EphB4 selective inhibitor could abrogate this acquired mechanism of drug resistance due to an enhanced apoptotic effect in cisplatin-resistant xenografts. In summary, these results help to understand the mechanisms of acquired resistance to chemotherapy and provide important information for clinical treatment strategies.
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China; Department of Emergency, General Hospital of Chengdu Military Command Area, Chengdu 610083, Sichuan Province, PR China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Shuqian
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Guihong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Qiaoyu
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China. Electronic address: w_jinjin@126.com.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D064593:Heterografts; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009368:Neoplasm Transplantation; D036224:Receptor, EphB4 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D036224:Receptor, EphB4; D002945:Cisplatin
keywords: A375; Cisplatin; EphB4; Melanoma