Activation of mTORC1 under nutrient starvation conditions increases cellular radiosensitivity in human liver cancer cell lines, HepG2 and HuH6
Activation of mTORC1 under nutrient starvation conditions increases cellular radiosensitivity in human liver cancer cell lines, HepG2 and HuH6
复制标题
DOI：
10.1016/j.bbrc.2015.11.016
复制
发表时间：
2015-12-25
影响因子：
3.1
通讯作者：
Hosoi, Yoshio
中科院分区：
文献类型：
--
作者：
Murata, Yasuhiko;Uehara, Yoshihiko;Hosoi, Yoshio
背景资料：在缺氧和营养饥饿条件下，含有细胞的未灌注区域的存在有助于人类实体肿瘤的辐射抗性。众所周知，缺氧引起细胞的辐射抗性。然而，营养饥饿条件对细胞辐射敏感性的影响尚不清楚。方法：人肝癌细胞系HepG2和HuH6，以及SV40转化的人成纤维细胞系，LM217检测营养饥饿条件对细胞辐射敏感性和哺乳动物雷帕霉素靶蛋白复合物1（mTORC 1）活性的影响。结果：与LM217细胞在营养饥饿条件下mTORC1活性受抑制相比，HepG2和HuH6细胞在营养饥饿条件下mTORC1活性升高。在所有三种细胞系中，在营养饥饿条件下AMP活化蛋白激酶（AMPK）和Akt都被激活。在饥饿条件下，观察到增加的辐射敏感性在HepG2和HuH6细胞中，在LM217细胞中的辐射敏感性降低。敲低mTOR使用siRNA的mTOR或治疗与mTOR抑制剂，雷帕霉素，抑制饥饿条件下增加的放射敏感性在HepG2 cells.Conclusion：我们的数据显示，第一次，营养饥饿条件下激活mTORC1和增加放射敏感性通过mTORC1激活肝癌细胞系，HepG2和HuH6。(C)2015 Elsevier Inc. All rights reserved.
Background: The presence of unperfused regions containing cells under hypoxic and nutrient starvation conditions contributes to radioresistance in solid human tumors. It is well known that the hypoxia causes cellular radioresistance. However, the effects of nutrient starvation conditions on cellular radiosensitivity remain unclear.Methods: Human liver cancer cell lines, HepG2 and HuH6, and a SV40-transformed human fibroblast cell line, LM217 were used to examine the effects of nutrient starvation conditions on cellular radiosensitivity and on activity of mammalian target of rapamycin complex 1 (mTORC1) that senses cellular nutrient conditions and affects radiosensitivity.Results: In contrast to suppressed mTORC1 activity under nutrient starvation conditions in LM217, HepG2 and HuH6 cells showed increased mTORC1 activity under nutrient starvation conditions. Both AMP-activated protein kinase (AMPK) and Akt were activated under nutrient starvation conditions in all the three cell lines. Under starvation conditions, increased radiosensitivity was observed in HepG2 and HuH6 cells, in contrast to decreased radiosensitivity in LM217 cells. Knockdown of mTOR using siRNA for mTOR or treatment with a mTOR inhibitor, rapamycin, suppressed the increased radiosensitivity under starvation conditions in HepG2 cells.Conclusion: Our data show for the first time that nutrient starvation conditions activate mTORC1 and increase radiosensitivity through mTORC1 activation in liver cancer cell lines, HepG2 and HuH6. (C) 2015 Elsevier Inc. All rights reserved.