Zhang, Xiang-Hua; Shin, Jung-Young; Kim, Jeong-Oh; Oh, Ji-Eun; Yoon, Seong-Ae; Jung, Chan-Kwon; Kang, Jin-Hyoung
Cancer letters
2012Sep ; 322 ( 2 ) :213-22.
PMID : 22433711
저자 상세정보
Zhang, Xiang-Hua -
Shin, Jung-Young -
Kim, Jeong-Oh -
Oh, Ji-Eun -
Yoon, Seong-Ae -
Jung, Chan-Kwon -
Kang, Jin-Hyoung -
ABSTRACT
Studies on non-small cell lung cancer (NSCLC) patients with KRAS or BRAF mutations are urgently needed to improve clinical outcomes. We evaluated the cytotoxicities of paclitaxel and sorafenib alone and in combination in NSCLC cell lines with KRAS or BRAF mutations and investigated the mechanism of the interaction between the drugs. We found synergistic antitumor efficacy with paclitaxel followed by sorafenib in in vitro and in vivo models of NSCLC. And, we determined that downregulation of the phosphorylated ERK and Rb, and Mcl-1 plays a critical role in the synergistic activity of the drugs. Further clinical trials are needed to verify the antitumor efficacy of this combination. CI - Copyright ??2012 Elsevier Ireland Ltd. All rights reserved.
Animals; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use; Apoptosis/drug effects; Benzenesulfonates/administration & dosage; Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics; Cell Cycle/drug effects; Cell Line, Tumor; Cell Proliferation/drug effects; Drug Synergism; Female; Gene Expression Regulation, Neoplastic/drug effects; Humans; Lung Neoplasms/*drug therapy/*genetics; Mice; Mice, Inbred BALB C; Mice, Nude; Mutation; Paclitaxel/administration & dosage; Proto-Oncogene Proteins B-raf/*genetics; Proto-Oncogene Proteins c-bcl-2/genetics; Pyridines/administration & dosage; Retinoblastoma Protein/genetics; Signal Transduction/drug effects; Tumor Suppressor Protein p53/genetics; Xenograft Model Antitumor Assays; ras Proteins/*genetics
MESH
Animals, Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use, Apoptosis/drug effects, Benzenesulfonates/administration & dosage, Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics, Cell Cycle/drug effects, Cell Line, Tumor, Cell Proliferation/drug effects, Drug Synergism, Female, Gene Expression Regulation, Neoplastic/drug effects, Humans, Lung Neoplasms/*drug therapy/*genetics, Mice, Mice, Inbred BALB C, Mice, Nude, Mutation, Myeloid Cell Leukemia Sequence 1 Protein, Niacinamide/analogs & derivatives, Paclitaxel/administration & dosage, Phenylurea Compounds, Proto-Oncogene Proteins B-raf/*genetics, Proto-Oncogene Proteins c-bcl-2/genetics, Pyridines/administration & dosage, Retinoblastoma Protein/genetics, Signal Transduction/drug effects, Tumor Suppressor Protein p53/genetics, Xenograft Model Antitumor Assays, ras Proteins/*genetics
링크