Calpain-2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme.
Calpain-2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme.
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Calpain-2抑制剂治疗优先降低表达该酶最高水平的人类结肠癌细胞的肿瘤进展。
DOI：
10.1002/cam4.1260
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发表时间：
2018-01
期刊：
影响因子：
4
通讯作者：
Hoffmann PR
中科院分区：
文献类型：
--
作者：
Marciel MP;Rose AH;Martinez V;Horio DT;Hashimoto AS;Hoffmann FW;Bertino P;Hoffmann PR
Calpain-2水平在对化疗耐药的结直肠肿瘤中较高，先前的工作表明calpain-2抑制剂治疗减少了炎症驱动的结直肠癌，但抑制剂对结肠癌细胞本身的直接影响尚未得到证实。在本研究中，用钙蛋白酶-2抑制剂直接处理5种人结肠癌细胞系，结果显示5种细胞系中有4种细胞系的细胞死亡增加，所有细胞系的非锚定依赖性生长减少。当检测钙蛋白酶-2水平时，三种细胞系显示出这种酶的水平增加：HCT 15（低），HCC 2998（中）和HCT 116（显著更高）。这与凝胶迁移试验一致，表明钙蛋白酶-2抑制剂在HCT 116细胞中最有效地减少了NF-κB核转位。对于这三种细胞系，使用荧光素酶表达细胞的直肠内移植来评价钙蛋白酶-2抑制剂在体内阻碍肿瘤进展的能力。结果显示，钙蛋白酶-2抑制剂治疗仅在注射HCT 116细胞的小鼠中减少肿瘤生长并增加存活率。这些数据表明，钙蛋白酶-2抑制剂治疗可能对表达最高水平钙蛋白酶-2的结直肠肿瘤最有效。
Calpain‐2 levels are higher in colorectal tumors resistant to chemotherapy and previous work showed calpain‐2 inhibitor therapy reduced inflammation‐driven colorectal cancer, but direct effects of the inhibitor on colon cancer cells themselves were not demonstrated. In the present study, five human colon cancer cell lines were directly treated with a calpain‐2 inhibitor and results showed increased cell death in 4 of 5 cell lines and decreased anchorage‐independent growth for all cell five lines. When tested for levels of calpain‐2, three cell lines exhibited increasing levels of this enzyme: HCT15 (low), HCC2998 (medium), and HCT116 (significantly higher). This was consistent with gel shift assays showing that calpain‐2 inhibitor reduced of NF‐κB nuclear translocation most effectively in HCT116 cells. Ability of calpain‐2 inhibitor to impede tumor progression in vivo was evaluated using intrarectal transplant of luciferase‐expressing cells for these three cell lines. Results showed that calpain‐2 inhibitor therapy reduced tumor growth and increased survival only in mice injected with HCT116 cells. These data suggest calpain‐2 inhibitor treatment may be most effective on colorectal tumors expressing highest levels of calpain‐2.
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影响因子：
7
作者：
Konze, Sarah A.;van Diepen, Laura;Buettner, Falk F. R.
通讯作者：
Buettner, Falk F. R.
影响因子：
0.7
作者：
Ivanova, E. V.;Kondakova, I. V.;Cheremisina, O. V.
通讯作者：
Cheremisina, O. V.
影响因子：
4.8
作者：
Huang, Zhi;Hoffmann, Fukun W.;Hoffmann, Peter R.
通讯作者：
Hoffmann, Peter R.
影响因子：
3
作者：
Thorpe, Hannah;Akhlaq, Maham;Ilyas, Mohammad
通讯作者：
Ilyas, Mohammad
基于新型生物信息学的方法，用于蛋白质组学生物标志物预测Calpain-2和caspase-3蛋白酶碎片化：应用于βII-光谱蛋白。
影响因子：
4.6
作者：
El-Assaad A;Dawy Z;Nemer G;Kobeissy F
通讯作者：
Kobeissy F