Wang Yang, Li Yezhou, Yang Li, Yin Dexin
Department of Gastroenterology, FAW General Hospital, Changchun, Jilin 130011, P.R. China.
Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Oncol Rep. 2017 Jul;38(1):591-597. doi: 10.3892/or.2017.5679. Epub 2017 May 30.
Low dose irradiation (LDIR) induces hormesis and adaptive response in organism and mammalian cell lines. Notably, LDIR generates distinct biological effects in cancer cells from normal cells, e.g., it may affect the growth of cancer cells via the activation of certain cell signaling pathway, which does not exist in normal cells. Therefore, LDIR is considered as a promising assistant method of clinical cancer therapy. In this study, we chose human colorectal adenocarcinoma cell line HT-29 as the experimental model, and investigated the differential biological effects between 250 mGy single dose LDIR and 250 mGy intermittent LDIR pretreatments in high dose irradiation (HDIR) radiotherapy and 5-fluorouracil (5-FU) based chemotherapy. Through the cell growth assays, we observed that 250 mGy intermittent LDIR pretreatment significantly increased the killing effect of both radiotherapy and chemotherapy. Western blotting results showed that intermittent LDIR pretreatment apparently activated the ATM/p53 (ataxia telangiectasia mutated, ATM) pathway in radiotherapy; it also activated ERK and p38MAPK pathways in chemotherapy. When we used chemical inhibitors to block the ATM/p53 or p38MAPK pathways, the intermittent LDIR induced cell growth inhibitions were reversed. However, blockage of ERK pathway could not affect the cell growth inhibiton in chemotherapy. Taken together, our findings evaluated the intermittent LDIR as a potential valuable method that can enhance the effectiveness of radiotherapy and chemotherapy, especially in the radio- or chemo-resistant tumor types.
低剂量辐射（LDIR）可诱导生物体和哺乳动物细胞系产生兴奋效应和适应性反应。值得注意的是，LDIR在癌细胞中产生的生物学效应与正常细胞不同，例如，它可能通过激活正常细胞中不存在的某些细胞信号通路来影响癌细胞的生长。因此，LDIR被认为是一种有前景的临床癌症治疗辅助方法。在本研究中，我们选择人结肠腺癌细胞系HT-29作为实验模型，研究了250 mGy单次剂量LDIR和250 mGy间歇LDIR预处理在高剂量辐射（HDIR）放疗和基于5-氟尿嘧啶（5-FU）的化疗中的差异生物学效应。通过细胞生长试验，我们观察到250 mGy间歇LDIR预处理显著增强了放疗和化疗的杀伤效果。蛋白质印迹结果显示，间歇LDIR预处理在放疗中明显激活了ATM/p53（共济失调毛细血管扩张症突变基因，ATM）通路；在化疗中它还激活了ERK和p38MAPK通路。当我们使用化学抑制剂阻断ATM/p53或p38MAPK通路时，间歇LDIR诱导的细胞生长抑制作用被逆转。然而，阻断ERK通路并不影响化疗中的细胞生长抑制作用。综上所述，我们的研究结果评估了间歇LDIR作为一种潜在的有价值的方法，它可以提高放疗和化疗的有效性，特别是在对放疗或化疗耐药的肿瘤类型中。
