title: HMGB1 Enhances Drug Resistance and Promotes In Vivo Tumor Growth of Lung Cancer Cells.
abstract: Drug resistance is an obstacle in the chemotherapeutic treatment of lung cancers. In the present study, the effects of high-mobility group box 1 (HMGB1) protein in chemotherapeutic resistance and the relationships between HMGB1 and chemotherapy drug-induced cell apoptosis or necrosis were clarified. We used cisplatin-sensitive A549 cells and cisplatin-resistant A549/DDP cells as cell models with IC50 of 11.58 and 46.95 μM, respectively. A549/DDP had higher level of HMGB1 compared with A549 cells. Interestingly, with the increasing concentration of DDP, HMGB1 was gradually located into cytoplasm in cisplatin-sensitive A549 cells. Moreover, interference with endogenous HMGB1 sensitized the effects of chemotherapeutic drugs, including 5-Fu, DDP, and OXA. Furthermore, results from an in vivo tumorigenesis experiment demonstrated that serum concentration of HMGB1 was much lower in the group inoculated with HMGB1 shRNA-transfected A549 cells than in the N.C. shRNA-transfected A549 inoculated group, as well as the tumor volume, suggesting that serum HMGB1 contributed to tumor growth in a mouse model. In conclusion, higher levels of HMGB1 probably contributed to chemotherapy drug resistance, and higher serum concentration of HMGB1 promoted in vivo tumor growth. The study would provide new clues to overcome drug resistance in chemotherapy of human lung cancers.
authors.affiliation: 1 Department of Respiration, The First Central Hospital of Tianjin , Tianjin, China .
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: 1 Department of Respiration, The First Central Hospital of Tianjin , Tianjin, China .
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Chen
authors.affiliation: 1 Department of Respiration, The First Central Hospital of Tianjin , Tianjin, China .
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.affiliation: 1 Department of Respiration, The First Central Hospital of Tianjin , Tianjin, China .
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: 2 Tianjin Institute of Medical Sciences , Tianjin, China .
authors.forename: Ling
authors.initials: L
authors.lastname: Yuan
authors.affiliation: 2 Tianjin Institute of Medical Sciences , Tianjin, China .
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Shen
authors.affiliation: 1 Department of Respiration, The First Central Hospital of Tianjin , Tianjin, China .
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Zhao
authors.affiliation: 1 Department of Respiration, The First Central Hospital of Tianjin , Tianjin, China .
authors.forename: Pan-Feng
authors.initials: PF
authors.lastname: Chen
authors.affiliation: 1 Department of Respiration, The First Central Hospital of Tianjin , Tianjin, China .
authors.forename: Min
authors.initials: M
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
chemical_list: D000970:Antineoplastic Agents; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D002945:Cisplatin
keywords: HMGB1; chemotherapy drug resistance; cisplatin; lung cancer