Preoperative low dose NSAID treatment influences the genes for stemness, growth, invasion and metastasis in colorectal cancer.
Preoperative low dose NSAID treatment influences the genes for stemness, growth, invasion and metastasis in colorectal cancer.
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DOI：
10.3892/ijo.2014.2686
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发表时间：
2014-12
影响因子：
5.2
通讯作者：
Lundholm K
中科院分区：
文献类型：
--
作者：
Lönnroth C;Andersson M;Asting AG;Nordgren S;Lundholm K
临床前数据以及越来越多的临床研究列表表明抗炎药对结直肠肿瘤的生物学有利。我们早些时候已经报道了三天的结直肠癌患者的术前治疗后重新表达活化的免疫细胞，随机接受口服NSAID（吲哚美辛或celebrex）。向所有患者提供了防止预防症（Esomeprasol），并用作假治疗。与MHC基因座激活一致，prominin1/cd133是与几种实体瘤相关的标记和预后不良的标记，被下调。本研究的目的是评估属于干细胞生态位，Oct4，Sox2和BMP7的其他调节剂的表达，以及一些微N，据报道充当肿瘤抑制剂或oncomirs。通过微阵列，定量实时PCR和免疫组织化学（IHC）分析可术的肿瘤活检。 NSAID（p <0.01）以及肿瘤抑制器miR-630（p <0.01）增加了干细胞主调节器SOX2（P <0.01），而BMP7（CRC中不良预后的标记）被NSAID下调（Indomethacin，p indomethacin，p <0.02）。 SOX2的上调，但没有其异二聚体结合伴侣Oct4的上调，可能意味着负馈回循环，并在肿瘤细胞的干性保留下开关。这得到了对随后事件的基因表达谱的总体评估，这表明NSAID治疗后攻击性较少。
Preclinical data, and an increasing list of clinical investigations, show anti-inflammatory agents to favourably influence the biology of colorectal tumor. We have earlier reported on re-expression of activated immune cells after three days preoperative treatment of patients with colorectal carcinoma, randomized to receive oral NSAID (indomethacin or celebrex). Antisecretory prophylaxis (esomeprasol) was provided to all patients and served as sham treatment. Concomittant to MHC locus activation, Prominin1/CD133, a marker associated with stemness and poor prognosis in several solid tumors, was downregulated. The aim of the present study was to evaluate expression of additional regulators belonging to the stem cell niche, OCT4, SOX2 and BMP7, as well as some microRNAs, reported to act as tumor suppressors or oncomiRs. Peroperative tumor biopsies were analyzed by microarrays, quantitative real-time PCR and immunohistochemistry (IHC). The stem cell master regulator SOX2 was increased by NSAIDs (p<0.01), as well as the tumor suppressor miR-630 (p<0.01), while BMP7, a marker for poor prognosis in CRC, was downregulated by NSAID (indomethacin, p<0.02). The upregulation of SOX2, but not of its heterodimer binding partner OCT4, could imply a negative feed-back loop, with a switch-off for stemness preservation of tumor cells. This is supported by the overall evaluation of gene expression profiles with subsequent events, indicating less aggressive tumors following NSAID treatment.
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影响因子：
37.3
作者：
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通讯作者：
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