ROLE OF PEROXIREDOXIN I IN RECTAL CANCER AND RELATED TO p53 STATUS
ROLE OF PEROXIREDOXIN I IN RECTAL CANCER AND RELATED TO p53 STATUS
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DOI：
10.1016/j.ijrobp.2010.05.025
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发表时间：
2010-11-01
影响因子：
7
通讯作者：
Wang, Jeng-Yi
中科院分区：
文献类型：
--
作者：
Chen, Miao-Fen;Lee, Kuan-Der;Wang, Jeng-Yi
背景：新辅助放化疗被广泛接受用于治疗局限性直肠癌。尽管过氧化还蛋白I(PrxI)和P53与肿瘤的发生和治疗有关，但PrxI及其与P53的相互作用在直肠癌预后和治疗反应中的作用仍未见报道。方法与材料：本研究采用膜阵列技术检测直肠癌患者PrxI和P53的表达水平，并与正常人群进行比较。为了阐明PrxI表达调控后的生物学变化，我们用PrxI沉默载体建立了稳定的野生型p53细胞株HCT-116和突变型p53细胞株HT-29。结果：膜阵列和免疫组织化学染色数据显示PrxI与肿瘤负担显著相关，而P53与肿瘤负担无关。我们的免疫化学结果进一步表明PrxI阳性与新辅助治疗的不良反应和较差的存活率有关。在细胞和动物实验中，PrxI的抑制显著地抑制了肿瘤的生长，并使肿瘤对辐射敏感，这表明PrxI清除活性氧的能力较低，并导致更广泛的DNA损伤。PrxI基因敲除后Hct-116和HT-29的差异可能与P53基因的表达有关。结论：根据我们的数据，PrxI结合P53基因的表达水平与患者的预后和治疗反应有关。我们认为PrxI可能是直肠癌的一个新的生物标志物。(C)2010年爱思唯尔公司。
Background: Neoadjuvant chemoradiotherapy is widely accepted for the treatment of localized rectal cancer. Although peroxiredoxin I (PrxI) and p53 have been implicated in carcinogenesis and cancer treatment, the role of PrxI and its interaction with p53 in the prognosis and treatment response of rectal cancer remain relatively unstudied.Methods and Materials: In the present study, we examined the levels of PrxI and p53 in rectal cancer patients using membrane arrays and compared them with normal population samples. To demonstrate the biologic changes after manipulation of PrxI expression, we established stable transfectants of HCT-116 (wild-type p53) and HT-29 (mutant p53) cells with a PrxI silencing vector. The predictive capacities of PrxI and p53 were also assessed by relating the immunohistochemical staining of a retrospective series of rectal cancer cases to the clinical outcome.Results: The membrane array and immunochemical staining data showed that PrxI, but not p53, was significantly associated with the tumor burden. Our immunochemistry findings further indicated that PrxI positivity was linked to a poor response to neoadjuvant therapy and worse survival. In cellular and animal experiments, the inhibition of PrxI significantly decreased tumor growth and sensitized the tumor to irradiation, as indicated by a lower capacity to scavenge reactive oxygen species and more extensive DNA damage. The p53 status might have contributed to the difference between HCT-116 and HT-29 after knockdown of PrxI.Conclusion: According to our data, the level of PrxI combined with the p53 status is relevant to the prognosis and the treatment response. We suggested that PrxI might be a new biomarker for rectal cancer. (C) 2010 Elsevier Inc.