کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2552020 1560694 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Actin-sequestering protein, thymosin beta-4, induces paclitaxel resistance through ROS/HIF-1α stabilization in HeLa human cervical tumor cells
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Actin-sequestering protein, thymosin beta-4, induces paclitaxel resistance through ROS/HIF-1α stabilization in HeLa human cervical tumor cells
چکیده انگلیسی

AimsWe investigated whether actin-sequestering protein, thymosin beta-4 (TB4)-induced reactive oxygen species (ROS) affect the stabilization of hypoxia-inducible transcription factor (HIF)-1α and paclitaxel-resistance induction.Main methodsHeLa human cervical tumor cells were used. The percentage of cell survival was determined by MTT assay. ROS production, cell cycle and hypodiploid cell formation were assessed by flow cytometry analysis. HIF-1α stabilization and molecular changes were analyzed by western blotting or RT-PCR. NF-κB activation was assessed by EMSA and western blotting.Key findingsTB4 protein (TB4P) significantly increased intracellular ROS level and HIF-1α. The increased level of HIF-1α by TB4P was reduced by the treatment with N-acetylcysteine (NAC), a well-known ROS scavenger. TB4P-induced ROS production was confirmed by the activation of nuclear factor kappa B. TB4P-induced Erk phosphorylation was attenuated by the treatment with NAC. In addition, tumor cell death was decreased by TB4 gene overexpression and TB4P treatment. NAC treatment attenuated tumor cell density increased by TB4P. Tumor cell death by paclitaxel was also increased by NAC treatment or the transfection with HIF-1α-siRNA. Paclitaxel-induced B16F10 mouse melanoma regression was physiologically inhibited in TB4-transgenic mice compared to wildtype mice.SignificanceThese findings demonstrate that TB4-induced ROS and ROS-mediated HIF-1α stabilization could play a role in tumor cell resistance to anticancer agents like paclitaxel. It suggests that soluble TB4 could be a novel endogenous regulator to control intracellular ROS production in tumor cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 87, Issues 9–10, 28 August 2010, Pages 286–293
نویسندگان
, ,