Department of Health Technology and Informatics, Faculty of Health and Social Science, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.
Biochem Biophys Res Commun. 2019 Sep 17;517(2):193-200. doi: 10.1016/j.bbrc.2019.07.043. Epub 2019 Jul 19.
Colorectal cancer is a common cancer with metachronous distant metastases still threatening overall survival. Tumor oxygen level influences tumor radiosensitivity in relation to autophagy and apoptosis. The objective of this study is to evaluate the expression and interaction between multiple key regulators in different oxygen levels. Human colorectal adenocarcinoma HT-29 cells were cultured in 1% or 10% oxygen level and irradiated by 2 Gy with different incubation time. Autophagy key regulators, AMPK, HIFs and JNK were evaluated by Western blot. Sequential autophagy key regulator activation was observed in the order of AMPK, HIF-1α, HIF-2α and JNK. 10% oxygen level could promote autophagy with similar degree of autophagy activation as 1% oxygen level in 48-h while irradiation could slightly inhibit autophagy. The results of this study supported prior evaluation of oxygen level and autophagy regulators for improving treatment efficacy and indicated the possible directions in developing individualized radiotherapy by selective targeting of hypoxic regions.
结直肠癌是一种常见的癌症，其异时性远处转移仍然威胁着总体生存率。肿瘤氧水平影响肿瘤放射敏感性，与自噬和细胞凋亡有关。本研究的目的是评估不同氧水平下多个关键调节剂的表达和相互作用。将人结直肠腺癌 HT-29 细胞在 1%或 10%氧水平下培养，并以不同的孵育时间用 2Gy 照射。通过 Western blot 评估自噬关键调节剂 AMPK、HIFs 和 JNK。观察到自噬关键调节剂的顺序激活，即 AMPK、HIF-1α、HIF-2α 和 JNK。10%氧水平可促进自噬，在 48 小时内与 1%氧水平的自噬激活程度相似，而照射可轻微抑制自噬。本研究的结果支持了先前对氧水平和自噬调节剂的评估，以提高治疗效果，并为通过选择性靶向缺氧区域开发个体化放疗指明了可能的方向。
