The synergistic effects of low dose fluorouracil and TRAIL on TRAIL-resistant human gastric adenocarcinoma AGS cells.
The synergistic effects of low dose fluorouracil and TRAIL on TRAIL-resistant human gastric adenocarcinoma AGS cells.
复制标题
小剂量氟尿嘧啶与TRAIL对TRAIL耐药人胃癌AGS细胞的协同作用
DOI：
10.1155/2013/293874
复制
发表时间：
2013
影响因子：
--
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Zhu H;Huang M;Ren D;He J;Zhao F;Yi C;Huang Y
肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis-inducing ligand，TRAIL）是肿瘤坏死因子家族的一员，由于其能诱导恶性肿瘤细胞凋亡而不损伤正常细胞而受到广泛关注。然而，许多癌细胞仍然对TRAIL具有耐药性。本研究探讨了低剂量氟尿嘧啶（5-Fu）联合TRAIL对TRAIL耐药的人胃腺癌AGS细胞的协同作用及其可能机制。用磺酰罗丹明B（SR B）法测定细胞活力，用金氏公式评价协同效应，并用倒置显微镜观察细胞形态学变化和流式细胞术进行验证。Western blotting检测TRAIL-R1（死亡受体4，DR 4）、TRAIL-R2（DR 5）、TRAIL-R3（诱骗受体，DcR 1）、TRAIL-R4（DcR 2）、caspase-3、caspase-8、caspase-9的表达。结果表明，低剂量5-Fu和TRAIL对TRAIL耐药的AGS细胞有明显的协同作用，这种协同作用可能是通过降低DcR 2的表达和增加DR 5的表达来实现的。内源性和外源性凋亡途径均被激活。提示小剂量5-Fu联合TRAIL治疗胃癌是一种有效的治疗方法。
The TNF-related apoptosis-inducing ligand (TRAIL) is a TNF family member which has been under intense focus because of its remarkable ability to induce apoptosis in malignant human cells while leaving normal cells unscathed. However, many cancer cells remain resistant to TRAIL. In this study, we had investigated the synergistic effects of low dose fluorouracil (5-Fu) and TRAIL on TRAIL-resistant human gastric adenocarcinoma AGS cells and explored the potential mechanisms. Cell viability was analyzed by sulforhodamine B (SRB) assay and the synergistic effects were evaluated by Jin's formula and confirmed by both morphological changes under inverted microscope and flow cytometry. The expression of TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (DR5), TRAIL-R3 (decoy receptor, DcR1), TRAIL-R4 (DcR2), procaspase-3, procaspase-8, and procaspase-9 was detected by western blotting. Our results showed that there were significant synergistic effects of low dose 5-Fu and TRAIL on TRAIL-resistant AGS cells, and this effect was supposed to be mediated by decreasing DcR2 expression and increasing DR5 expression. The extrinsic and intrinsic apoptosis pathways were both activated. The data suggest that combined treatment of low dose 5-Fu and TRAIL can be an effective therapeutic approach for gastric adenocarcinoma.
登录
查看更多内容
影响因子：
11.2
作者：
Prasad S;Yadav VR;Ravindran J;Aggarwal BB
通讯作者：
Aggarwal BB
影响因子：
5
作者：
Holoch, Peter A.;Griffith, Thomas S.
通讯作者：
Griffith, Thomas S.
影响因子：
12.4
作者：
Morizot, A.;Merino, D.;Micheau, O.
通讯作者：
Micheau, O.
影响因子：
12.4
作者：
Ganten, TM;Haas, TL;Walczak, H
通讯作者：
Walczak, H
影响因子：
7.2
作者：
Ahmed, Firoj;Toume, Kazufumi;Ishibashi, Masami
通讯作者：
Ishibashi, Masami