Wu Szu-Yuan, Liu Yi-Wen, Wang Yang-Kao, Lin Tsung-Hsing, Li Yi-Zhen, Chen Shu-Hsin, Lee Ying-Ray
Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
J BUON. 2014 Jan-Mar;19(1):137-44.
Irradiation-induced autophagy has been reported in several types of cancers, however, the relationship between irradiation and autophagy in human oral squamous cell carcinoma (OSCC) has not yet been described. In this study we investigated the induction of autophagy in cell lines by exposing them to ionizing irradiation.
Human OSCC OC3 and SAS cell lines were used in this study. Cell viability and induction of autophagy were determined under irradiation treatment. The GFP-LC3 puncta formation and the levels of LC3-II as indicators of autophagy were detected by fluorescence microscopy and Western blot method. The signaling pathways involved in irradiation-mediated autophagy were also determined by Western blot method.
Irradiation decreased cell viability only in OC3 cells, while autophagic machinery and related signaling pathways were found to be elevated after irradiation in OC3 and SAS cells. However, autophagic degradation determined by the reduction of p62 levels was only found in OC3 cells, suggesting autophagosome accumulation took place in SAS cells. In addition, irradiation accompanied with rapamycin treatment elevated autophagy formation and induced death of OC3 cells.
These results suggested that induction of autophagy might provide an advantageous strategy to increase the anticancer effects of radiotherapy in patients with OSCCs.
已有报道称几种癌症中存在辐射诱导的自噬，然而，人类口腔鳞状细胞癌（OSCC）中辐射与自噬之间的关系尚未见描述。在本研究中，我们通过将细胞系暴露于电离辐射来研究自噬的诱导情况。
本研究使用了人类OSCC的OC3和SAS细胞系。在辐射处理下测定细胞活力和自噬的诱导情况。通过荧光显微镜和蛋白质印迹法检测作为自噬指标的GFP-LC3斑点形成和LC3-II水平。还通过蛋白质印迹法确定了辐射介导的自噬所涉及的信号通路。
辐射仅在OC3细胞中降低细胞活力，而在OC3和SAS细胞中发现辐射后自噬机制和相关信号通路升高。然而，仅在OC3细胞中发现通过p62水平降低确定的自噬降解，这表明SAS细胞中发生了自噬体积累。此外，辐射联合雷帕霉素处理可增加自噬形成并诱导OC3细胞死亡。
这些结果表明，诱导自噬可能为增强OSCC患者放疗的抗癌效果提供一种有利策略。
