Synergistic antitumor efficacy of sequentially combined paclitaxel with sorafenib in vitro and in vivo NSCLC models harboring KRAS or BRAF mutations

Autor: Jung-Young Shin, Seong-Ae Yoon, Ji Eun Oh, Chan Kwon Jung, Jin-Hyoung Kang, Jeong-Oh Kim, Xiang-Hua Zhang
Rok vydání: 2011
Předmět:
Oncology
Cancer Research
Lung Neoplasms
Pyridines
Apoptosis
medicine.disease_cause
Retinoblastoma Protein
chemistry.chemical_compound
Mice
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
Medicine
Mutation
Mice
Inbred BALB C
Benzenesulfonates
Cell Cycle
Drug Synergism
Sorafenib
Gene Expression Regulation
Neoplastic
Paclitaxel
Proto-Oncogene Proteins c-bcl-2
Female
KRAS
medicine.drug
Signal Transduction
Niacinamide
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Mice
Nude
Downregulation and upregulation
In vivo
Internal medicine
Cell Line
Tumor
Carcinoma
Animals
Humans
neoplasms
Cell Proliferation
business.industry
Phenylurea Compounds
medicine.disease
Xenograft Model Antitumor Assays
digestive system diseases
respiratory tract diseases
Clinical trial
chemistry
ras Proteins
Myeloid Cell Leukemia Sequence 1 Protein
Tumor Suppressor Protein p53
business
Zdroj: Cancer letters. 322(2)
ISSN: 1872-7980
Popis: 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.
Databáze: OpenAIRE
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