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首页> 外文期刊>Journal of Cellular Physiology >Fluoro-Sorafenib (Regorafenib) effects on hepatoma cells: Growth inhibition, quiescence, and recovery
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Fluoro-Sorafenib (Regorafenib) effects on hepatoma cells: Growth inhibition, quiescence, and recovery

机译:Fluoro-Sorafenib (Regorafenib)对肝癌的影响细胞:生长抑制、静止和复苏

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摘要

To evaluate the growth-inhibitory properties of the potent multi-kinase antagonist Regorafenib (Fluoro-Sorafenib), which was synthesized as a more potent Sorafenib, a Raf inhibitor and to determine whether similar mechanisms were involved, human hepatoma cell lines were grown in the presence or absence of Regorafanib and examined for growth inhibition. Western blots were performed for Raf targets, apoptosis, and autophagy. Regorafenib inhibited growth of human Hep3B, PLC/PRF/5, and HepG2 cells in a concentration- and time-dependent manner. Multiple signaling pathways were altered, including MAP kinases phospho-ERK and phospho-JNK and its target phospho-c-Jun. There was evidence for apoptosis by FACS, cleavage of caspases and increased Bax levels; as well as induction of autophagy, as judged by increased Beclin-1 and LC3 (II) levels. Prolonged drug exposure resulted in cell quiescence. Full growth recovery occurred after drug removal, unlike with doxorubicin chemotherapy. Regorafenib is a potent inhibitor of cell growth. Cells surviving Regorafenib treatment remain viable, but quiescent and capable of regrowth following drug removal. The reversibility of tumor cell growth suppression after drug removal may have clinical implications.
机译:评估的growth-inhibitory性质强有力的multi-kinase拮抗剂Regorafenib(Fluoro-Sorafenib)是合成更强有力的索拉非尼,英国皇家空军抑制剂和确定是否相似的机制,人类肝癌细胞系生长在Regorafanib的存在与否研究了抑制经济增长。为英国皇家空军进行目标、细胞凋亡和自噬。Hep3B、PLC /脉冲重复频率/ 5,HepG2细胞浓度和时间的方式。多个信号通路被改变,包括地图激酶phospho-ERK和phospho-JNKphospho-c-Jun及其目标。细胞凋亡的流式细胞仪,还和乳沟伯灵顿水平增加;自噬,根据Beclin-1和增加LC3 (II)的水平。在细胞静止。药物去除后,与阿霉素化疗。细胞生长。治疗仍然是可行的,但静和再生后药物的去除能力。肿瘤细胞生长抑制的可逆性后药物清除可能临床的影响。

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