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CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells.
Journal of Cell Communication and Signaling ( IF 3.6 ) Pub Date : 2020-03-21 , DOI: 10.1007/s12079-020-00558-3
Zhao-Jun Li 1, 2 , Ya-Jun Hou 3 , Gang-Ping Hao 2 , Xiao-Xuan Pan 2 , Hong-Rong Fei 1 , Feng-Ze Wang 2
Affiliation  

CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). In this study, we aimed to explore the anticancer effects of CUDC-907 on human breast cancer cells. Our results showed that CUDC-907 effectively inhibited breast cancer cell proliferation. Flow cytometry analysis revealed that CUDC-907 induced cell cycle arrest and apoptosis in breast cancer cells. The combined treatment of CUDC-907 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in a marked increase in apoptosis and cleavage of caspase-8, -9 and poly (ADP-ribose) polymerase (PARP) in breast cancer cells. CUDC-907 enhanced expressions of death receptor 5 (DR5), reduced the levels of anti-apoptotic molecules XIAP, Bcl-2 and Bcl-xL. Knockdown of DR5 abrogated apoptosis induced by the combination of CUDC-907 and TRAIL in breast cancer cells. CUDC-907 increased the phosphorylation of JNK and p38 MAPK. JNK inhibitor pretreatment attenuated CUDC-907-induced upregulation of DR5. In summary, CUDC-907 shows potent cytotoxicity against breast cancer cells and facilitates TRAIL-mediated apoptosis through DR5 upregulation. The combination of CUDC-907 and TRAIL may be a promising therapeutic approach in the treatment of breast cancer.

中文翻译:

CUDC-907通过上调DR5在乳腺癌细胞中增强TRAIL诱导的凋亡。

CUDC-907是磷酸肌醇3激酶(PI3K)和组蛋白脱乙酰基酶(HDAC)的新型双作用抑制剂。在这项研究中,我们旨在探讨CUDC-907对人乳腺癌细胞的抗癌作用。我们的结果表明,CUDC-907有效抑制了乳腺癌细胞的增殖。流式细胞仪分析表明,CUDC-907诱导了乳腺癌细胞的细胞周期停滞和凋亡。CUDC-907和肿瘤坏死因子相关的凋亡诱导配体(TRAIL)的联合治疗导致乳腺癌的凋亡和caspase-8,-9和聚(ADP-核糖)聚合酶(PARP)的裂解显着增加细胞。CUDC-907增强了死亡受体5(DR5)的表达,降低了抗凋亡分子XIAP,Bcl-2和Bcl-xL的水平。DR5的敲低废除了CUDC-907和TRAIL联合诱导的乳腺癌细胞凋亡。CUDC-907增加了JNK和p38 MAPK的磷酸化。JNK抑制剂预处理减弱了CUDC-907诱导的DR5上调。总之,CUDC-907对乳腺癌细胞显示出有效的细胞毒性,并通过DR5上调促进TRAIL介导的细胞凋亡。CUDC-907和TRAIL的组合可能是治疗乳腺癌的有前途的治疗方法。
更新日期:2020-04-21
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