JQ1, a BET-bromodomain inhibitor, inhibits human cancer growth and suppresses PD-L1 expression
JQ1, a BET-bromodomain inhibitor, inhibits human cancer growth and suppresses PD-L1 expression
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JQ1 是一种 BET 溴结构域抑制剂，可抑制人类癌症生长并抑制 PD-L1 表达
DOI：
10.1002/cbin.11139
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发表时间：
2019-06-01
影响因子：
3.9
通讯作者：
Chen, Rui
中科院分区：
文献类型：
--
作者：
Liu, Kaisheng;Zhou, Zhifan;Chen, Rui
传统的细胞毒性化疗药物溶解度差，毒性大。因此，有必要开发分子靶向药物。程序性死亡配体1 （Programmed death-ligand 1, PD-L1）与多种癌症的预后相关，阻断PD-1/PD-L1信号通路可增加抗肿瘤免疫的幅度。在本研究中，我们研究了一种溴域和外溴域抑制剂JQ1对肾癌原代培养细胞、前列腺癌、肝癌和肺癌细胞系细胞生长和PD-L1信使RNA （mRNA）和蛋白水平的影响。细胞计数试剂盒-8检测结果表明，JQ1抑制细胞生长呈剂量依赖性。在jq1处理的肾癌、前列腺癌、肝癌和肺癌细胞系原代培养中，PD-L1 mRNA和蛋白水平下降。此外，jq1处理的细胞中PD-L2的mRNA水平也有所下降。总之，JQ1可能是一种潜在的抗肿瘤药物。
Most traditional cytotoxic chemotherapeutic agents have poor aqueous solubility and significant toxicity. Hence, there is a need to develop molecule-targeted drugs. Programmed death-ligand 1 (PD-L1) is associated with the prognosis of several cancer types, and blockade of PD-1/PD-L1 signaling increases the amplitude of anti-tumor immunity. In the present study, we investigated the effects of JQ1, a bromodomain and extraterminal-bromodomain inhibitor, on cell growth, and messenger RNA (mRNA) and protein levels of PD-L1 in renal cell carcinoma primary culture cells, and prostate, liver, and lung cancer cell lines. The results of the cell counting kit-8 assay suggested that JQ1 inhibits cell growth in a dose-dependent manner. The mRNA and protein levels of PD-L1 decreased in the primary culture of JQ1-treated renal carcinoma, prostate cancer, liver cancer, and lung cancer cell lines. In addition, the mRNA level of PD-L2 also decreased in the JQ1-treated cells. Overall, JQ1 might be a potential anti-tumor agent.