title: Synergistic antitumor efficacy of sequentially combined paclitaxel with sorafenib in vitro and in vivo NSCLC models harboring KRAS or BRAF mutations.
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.
authors.affiliation: The Catholic University of Korea, Seoul, Republic of Korea. xhzn2007@gmail.com
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Zhang
authors.forename: Jung-Young
authors.initials: JY
authors.lastname: Shin
authors.forename: Jeong-Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Oh
authors.forename: Seong-Ae
authors.initials: SA
authors.lastname: Yoon
authors.forename: Chan-Kwon
authors.initials: CK
authors.lastname: Jung
authors.forename: Jin-Hyoung
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001557:Benzenesulfonates / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009536:Niacinamide / Q000031:analogs & derivatives; D017239:Paclitaxel / Q000008:administration & dosage; D010671:Phenylurea Compounds; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011725:Pyridines / Q000008:administration & dosage; D016160:Retinoblastoma Protein / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000235:genetics*
chemical_list: D001557:Benzenesulfonates; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010671:Phenylurea Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D009536:Niacinamide; D000077157:Sorafenib; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins; D017239:Paclitaxel