The major drawback of anticancer therapy is the development of resistance against drugs and radiation at the later phase of treatment which may lead to recurrences of the disease. Therefore, strategy was taken to enhance radiation sensitivity of lung (A549) and liver (HepG2) carcinoma cells by treatment with ferulic acid (FA) prior to irradiation. FA pre-treatment initially decreased reactive oxygen species (ROS) level in carcinoma cells which induced reductive stress and cytostasis. To overcome this stress, cellular mechanism increased the Keap1 level to down-regulate nuclear localisation of Nrf2 and its dependent antioxidant system. The antioxidant system reached the lowest level after 3 and 6 h of FA treatment in A549 and HepG2 cells respectively. As endogenous ROS were still being generated at same rate, ROS level was clearly higher than control which changed the reductive stress to oxidative stress. Exposure to γ-radiation in this condition further increased ROS level and caused radio-sensitisation of carcinoma cells. Combination of irradiation (IR) and FA activated mitochondrial apoptotic pathway and concomitantly inhibited the cell cycle progression and survival pathway over the IR group. Moreover, the combination treatment showed significant tumour regression, caspase 3 activation and nuclear fragmentation in tumour tissue compared to radiation alone. In contrast, FA pre-treatment protected peripheral blood mononuclear cells (PBMC) and normal lung fibroblast WI38 cells from radiation damage. Together, combination treatment offers effective strategy of killing cancer cells and demonstrates its potential for increasing the efficacy of radio-therapy.

中文翻译：

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阿魏酸通过折叠氧化还原稳态来增强肺和肝癌细胞的放射敏感性：Akt / p38 MAPK信号传导途径的机制参与。

抗癌疗法的主要缺点是在治疗的后期对药物和放射线产生抗药性，这可能导致疾病复发。因此，采取了通过在照射前用阿魏酸（FA）处理来增强肺（A549）和肝（HepG2）癌细胞的放射敏感性的策略。FA预处理最初会降低癌细胞中的活性氧（ROS）水平，从而诱导还原性应激和细胞停滞。为了克服这种压力，细胞机制提高了Keap1水平，以下调Nrf2及其相关抗氧化剂系统的核定位。分别在A549和HepG2细胞中，FA处理3小时和6小时后，抗​​氧化剂系统达到最低水平。由于内源性ROS仍以相同的速率生成，ROS水平明显高于对照，其将还原性应激转变为氧化性应激。在这种情况下暴露于γ射线会进一步提高ROS水平并引起癌细胞的放射增敏作用。辐射（IR）和FA的组合激活了线粒体的凋亡途径，并同时抑制了IR组的细胞周期进程和存活途径。此外，与单独的放射治疗相比，联合治疗在肿瘤组织中显示出显着的肿瘤消退，caspase 3活化和核碎裂。相反，FA预处理可保护外周血单核细胞（PBMC）和正常肺成纤维细胞WI38细胞免受辐射损伤。一起，