顺铂
A549电池
生物
体内
HMGB1
转染
癌症研究
抗药性
小发夹RNA
细胞凋亡
细胞培养
化疗
药理学
免疫学
基因敲除
微生物学
生物化学
炎症
生物技术
遗传学
作者
Hong Zheng,Jia-Ning Chen,Xi Yu,Ping Jiang,Ling Yuan,Hong-Sheng Shen,Lihong Zhao,Pan-Feng Chen,Min Yang
标识
DOI:10.1089/dna.2016.3360
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI