The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, 518020, Guangdong, China.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, 999077, Hong Kong SAR, China.
Cell Biol Int. 2019 Jun;43(6):642-650. doi: 10.1002/cbin.11139. Epub 2019 Apr 25.
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.
大多数传统的细胞毒性化疗药物水溶性差，毒性大。因此，需要开发针对特定分子的药物。程序性死亡配体 1（PD-L1）与多种癌症类型的预后相关，阻断 PD-1/PD-L1 信号通路会增加抗肿瘤免疫的幅度。在本研究中，我们研究了 JQ1（一种溴结构域和末端外结构域抑制剂）对肾癌细胞原代培养细胞以及前列腺癌、肝癌和肺癌细胞系的细胞生长以及 PD-L1 的信使 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 呈剂量依赖性抑制细胞生长。JQ1 处理的肾癌细胞、前列腺癌、肝癌和肺癌细胞系中原代培养的 PD-L1 mRNA 和蛋白水平下降。此外，JQ1 处理的细胞中 PD-L2 的 mRNA 水平也下降。总的来说，JQ1 可能是一种有潜力的抗肿瘤药物。
