Yan Chen, Luo Lan, Goto Shinji, Urata Yoshishige, Guo Chang-Ying, Doi Hanako, Kitazato Kaio, Li Tao-Sheng
Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Thoracic Surgery, Jiangxi Cancer Hospital, Nanchang, PR China.
Oncotarget. 2016 Jul 19;7(29):45112-45121. doi: 10.18632/oncotarget.8972.
Autophagy, an essential catabolic pathway of degrading cellular components within the lysosome, has been found to benefit the growth and therapeutic resistance of cancer cells. In this study, we investigated the role of autophagy in the radio-sensitivity of cancer stem cells. By separating CD44+/CD133+ cancer stem cells from parental HCT8 human colorectal cancer cells, we found a significantly higher level of autophagy in the CD44+/CD133+ cells than in the parental cells. Exposure to 5 Gy of γ-ray significantly damaged both CD44+/CD133+ cells and parental cells, but the radiation-induced damage did not differ between the groups. Unexpectedly, autophagy was not significantly induced by radiation exposure in the CD44+/CD133+ cells and parental cells. The inhibition of autophagy by the silencing of ATG7, a factor required for autophagy at the stage of autophagosome precursor synthesis, did not significantly change the growth and radiation-induced damage in both CD44+/CD133+ cells and parental cells. Although an enhanced basic level of autophagy was found in the CD44+/CD133+ cancer stem cells, our data suggest that the canonical autophagy in cancer cells plays few roles, if any, in radio-sensitivity.
自噬是一种在溶酶体内降解细胞成分的重要分解代谢途径，已发现其有利于癌细胞的生长和治疗抗性。在本研究中，我们调查了自噬在癌症干细胞放射敏感性中的作用。通过从亲代HCT8人结肠癌细胞中分离出CD44+/CD133+癌症干细胞，我们发现CD44+/CD133+细胞中的自噬水平显著高于亲代细胞。暴露于5 Gy的γ射线会显著损伤CD44+/CD133+细胞和亲代细胞，但两组之间辐射诱导的损伤没有差异。出乎意料的是，CD44+/CD133+细胞和亲代细胞在辐射暴露后自噬并未显著诱导。通过沉默ATG7（自噬体前体合成阶段自噬所需的一个因子）来抑制自噬，在CD44+/CD133+细胞和亲代细胞中均未显著改变其生长和辐射诱导的损伤。尽管在CD44+/CD133+癌症干细胞中发现自噬的基础水平有所增强，但我们的数据表明，癌细胞中的经典自噬在放射敏感性中几乎没有作用（如果有作用的话）。
