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

Zhang, Xiang-Hua; Shin, Jung-Young; Kim, Jeong-Oh; Oh, Ji-Eun; Yoon, Seong-Ae; Jung, Chan-Kwon; Kang, Jin-Hyoung

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

2012

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.

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Ключевые слова АГРОВОК

animals apoptosis carcinoma cell cycle clinical trials drug therapy drugs gene expression regulation genetics humans mice mice mice models mutation mutation niacinamide patients pharmacology pyridines

Библиографическая информация

Опубликовано в

Cancer letters

Том 322 Выпуск 2 Нумерация страниц 213 - 222 ISSN 0304-3835

Издатель

Elsevier Ltd

Другие темы

Tumor suppressor protein p53; Ras proteins; Paclitaxel; Lung neoplasms; Retinoblastoma protein; Proto-oncogene proteins b-raf; Inbred balb c; Non-small-cell lung; Neoplastic; Proto-oncogene proteins c-bcl-2; Cell line; Tumor; Female; Therapeutic use; Drug synergism; Antineoplastic combined chemotherapy protocols; Cell proliferation; Benzenesulfonates; Lung neoplasms; Administration & dosage; Signal transduction; Analogs & derivatives; Drug effects; Nude; Phenylurea compounds; Xenograft model antitumor assays; Paclitaxel; Myeloid cell leukemia sequence 1 protein

Язык

Английский

Тип

Journal Article; Text

В АГРИСе с: 2024-02-27

Формат: MODS

Поставщик данных

Эту запись предоставил National Agricultural Library

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Ссылки

DOI DOI http://dx.doi.org/10.1016/j.canlet.2012.03.015

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

2012

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Библиографическая информация