کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8546658 | 1561726 | 2018 | 36 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Dexamethasone alleviates pemetrexed-induced senescence in Non-Small-Cell Lung Cancer
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
دانش تغذیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Pemetrexed (PEM) is a novel and multi-targeted antifolate used as an antineoplastic agent for non-small cell lung cancer (NSCLC) and pleural mesothelioma. Although glucocorticoid was often used with PEM to reduce toxicity during the chemotherapy, it is not clear yet whether glucocorticoid co-administration could affect PEM efficacy in NSCLC. Here we established NSCLC cell lines and examined the effects of dexamethasone (DEX) on PEM sensitivity in vitro and in xenograft models. DEX co-administration reduced chemotherapy sensitivity to PEM in xenograft models. DEX co-administration promoted cell growth and weakened senescence growth arrest, such as altered secretions of proinflammatory and mitogenic cytokines, reminiscent of a senescence associate secretory phenotype (SASP). CSCs in DEX co-administration group were subsequently found to be less sensitive towards PEM treatment as measured by cell proliferation and generation of tumor spheres in the presence of PEM. Survival molecule B-cell lymphoma-2 (Bcl-2) may involve in this process and blockage of Bcl-2 could reverse altered senescence and CSCs abilities, thus alleviated PEM insensitivity. As such, DEX might suppress the antitumor activity of PEM through altered SASP level that had induced traits similar to CSCs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Food and Chemical Toxicology - Volume 119, September 2018, Pages 86-97
Journal: Food and Chemical Toxicology - Volume 119, September 2018, Pages 86-97
نویسندگان
Haiyan Ge, Jun Ke, Nuo Xu, Hongqing Li, Jin Gong, Xiangyang Li, Yuanlin Song, Huili Zhu, Chunxue Bai,