NGFR Increases the Chemosensitivity of Colorectal Cancer Cells by Enhancing the Apoptotic and Autophagic Effects of 5-fluorouracil via the Activation of S100A9.
NGFR Increases the Chemosensitivity of Colorectal Cancer Cells by Enhancing the Apoptotic and Autophagic Effects of 5-fluorouracil via the Activation of S100A9.
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NGFR 通过激活 S100A9 增强 5-氟尿嘧啶的凋亡和自噬作用，从而提高结直肠癌细胞的化疗敏感性
DOI：
10.3389/fonc.2021.652081
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发表时间：
2021
影响因子：
4.7
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Chen H;Huang J;Chen C;Jiang Y;Feng X;Liao Y;Yang Z
结直肠癌（CRC）目前是全球癌症相关死亡的第三大原因，基于5-氟尿嘧啶（5-FU）的化疗是CRC手术前后的重要辅助治疗。然而，CRC化疗的疗效受到化疗耐药性的限制，因此发现新的标记物来指示化疗敏感性是必不可少的。神经生长因子受体（NGFR）是一种细胞表面受体，参与细胞的死亡和存活。我们以前的研究表明NGFR作为一种肿瘤抑制因子，高表达与术后接受5-FU为基础的辅助化疗的患者的预后更好相关。本研究的目的是探讨NGFR对CRC化疗反应的影响。NGFR转染后，使用DLD 1和HCT 8细胞研究化疗敏感性。流式细胞术检测细胞凋亡。使用GFP-LC3B瞬时转染评估自噬。使用mRNA微阵列测量基因表达。Western blot检测Beclin-1和Bcl-2蛋白表达。应用免疫组化方法检测NGFR和S100钙结合蛋白A9（S100A9）在结直肠癌组织中的表达。结果显示，转染NGFR的DLD 1和HCT 8细胞经5-FU处理后，半数最大抑制浓度低于对照组，细胞活力低于空载体细胞。肿瘤大小也小于体内空载体细胞。NGFR转染细胞中凋亡和自噬细胞的百分比更高。5-FU处理后NGFR可上调S100A9的表达。Bcl-2和Beclin-1的结合被过表达的NGFR显著抑制。NGFR +/S100A9+患者的5年总体和无病生存率优于NGFR −/S100A9 −患者。本研究结果提示NGFR可作为预测结直肠癌患者化疗敏感性的指标。
Colorectal cancer (CRC) is currently the third leading cause of cancer-related deaths worldwide, and 5-fluorouracil (5-FU)-based chemotherapies serve as important adjuvant therapies before and after surgery for CRC. However, the efficacy of CRC chemotherapy is limited by chemoresistance, and therefore the discovery of novel markers to indicate chemosensitivity is essential. Nerve growth factor receptor (NGFR), a cell surface receptor, is involved in cell death and survival. Our previous study indicated that NGFR acts as a tumor suppressor, and high expression is associated with better outcomes in patients receiving 5-FU-based adjuvant chemotherapy after surgery. The aim of this study was to investigate the effect of NGFR on the chemotherapeutic response in CRC. Chemosensitivity was investigated using DLD1 and HCT8 cells after NGFR transfection. Apoptosis was investigated by flow cytometry. Autophagy was assessed using GFP-LC3B transient transfection. Gene expression was measured using an mRNA microarray. Beclin-1 and Bcl-2 protein expressions were assessed by western blot. NGFR and S100 calcium-binding protein A9 (S100A9) expressions in CRC patients were investigated by immunohistochemistry. The results showed that the half maximal inhibitory concentration of NGFR-transfected cells was lower than that of controls in DLD1 and HCT8 cells after 5-FU treatment, and cell viability was lower than in empty-vector cells. Tumor sizes were also smaller than in empty-vector cells in vivo. The percentages of apoptotic and autophagic cells were higher in NGFR-transfected cells. NGFR elevated the expression of S100A9 after 5-FU treatment. The combination of Bcl-2 and Beclin-1 was significantly suppressed by overexpressed NGFR. Five-year overall and disease-free survival in NGFR+/S100A9+ patients was better than in NGFR−/S100A9− patients. This study’s findings suggest that NGFR may serve as a marker predicting CRC patients’ chemosensitivity.
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影响因子：
9.8
作者：
Johnston AL;Lun X;Rahn JJ;Liacini A;Wang L;Hamilton MG;Parney IF;Hempstead BL;Robbins SM;Forsyth PA;Senger DL
通讯作者：
Senger DL
影响因子：
4.6
作者：
Khwaja, F;Djakiew, D
通讯作者：
Djakiew, D
影响因子：
4.8
作者：
Kerkhoff, C;Nacken, W;Doussiere, J
通讯作者：
Doussiere, J
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.bbamcr.2007.10.015
发表时间：
2008-02-01
影响因子：
5.1
作者：
Ghavami, Saeld;Kerkhoff, Claus;Los, Marek
通讯作者：
Los, Marek