title: Enhancing Therapeutic Efficacy of Cisplatin by Blocking DNA Damage Repair.
abstract: Self-repair of nuclear DNA damage is the most known reason that leads to drug resistance of cancer tissue and limited therapeutic efficacy of anticancer drugs. Inhibition of protein phosphatase 2A (PP2A) would block DNA damage-induced defense of cancer cells to suppress DNA repair for enhanced cancer treatment. Here, we combined a PP2A inhibitor LB (4-(3-carboxy-7-oxa-bicyclo[2.2.1]heptane-2-carbonyl) piperazine-1-carboxylic acidtert-butyl ester) and the DNA damage chemotherapeutic drug cisplatin through a simple physical superposition. The two drugs administrated at a ratio of 1:1 exhibited an optional synergistic antitumor efficacyin vitroandin vivo. LB was demonstrated to specifically activate the protein kinase B (Akt) and mitogen-activated protein kinases (MAPK) signaling pathways by PP2A inhibition to overcome cell cycle arrest caused by cisplatin-induced DNA damage.
authors: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China; University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
authors: Yuwei
authors: Y
authors: Cong
authors: Nanjing Orientleader Technology Co., Ltd. , Nanjing 210028, P. R. China.
authors: Liangyan
authors: L
authors: Wang
authors: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China; University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
authors: Zigui
authors: Z
authors: Wang
authors: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China; University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
authors: Shasha
authors: S
authors: He
authors: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors: Dongfang
authors: D
authors: Zhou
authors: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors: Xiabin
authors: X
authors: Jing
authors: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors: Yubin
authors: Y
authors: Huang
keywords: DNA repair; Protein phosphatase 2A; cisplatin; combination treatment