The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, Jiangsu Province, China.
Research Center for Clinical Oncology.
Anticancer Drugs. 2019 Jun;30(5):495-500. doi: 10.1097/CAD.0000000000000758.
Liver X receptors are recognized as important regulators of cholesterol, fatty acid metabolism, inflammatory responses, and glucose homeostasis. The antineoplastic properties of synthetic liver X receptor (LXR) agonists (T0901317 and GW3965) have been reported in human carcinomas. Epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) is a first-line treatment for non-small-cell lung cancer patients with EGFR mutations. We used scratch and transwell assays to analyze cell migration and invasion. We evaluated tumor migration and invasion in vitro using a fluorescent orthotopic lung cancer model. An MMP9 (mouse) enzyme-linked immunosorbent assay kit was used to measure serum MMP9 concentrations. Protein expression was identified by western blot assays. In this study, we determined the effects of T0901317 and/or an EGFR-TKI on the lung cancer cell lines A549 and HCC827-8-1 in vitro and in vivo. We confirmed that the combination of the LXR agonist T0901317 and gefitinib can inhibit the migration and invasion of lung cancer both in vivo and in vitro, and this effect was possibly achieved by the inhibition of the ERK/MAPK signaling pathway. Our study showed that the combination of the LXR agonist T0901317 and gefitinib can inhibit the migration and invasion of lung cancer both in vivo and in vitro.
肝 X 受体被认为是胆固醇、脂肪酸代谢、炎症反应和葡萄糖稳态的重要调节因子。合成肝 X 受体 (LXR) 激动剂 (T0901317 和 GW3965) 的抗肿瘤特性已在人类癌中得到报道。表皮生长因子酪氨酸激酶抑制剂 (EGFR-TKI) 是 EGFR 突变的非小细胞肺癌患者的一线治疗药物。我们使用划痕和 Transwell 分析来分析细胞迁移和侵袭。我们使用荧光原位肺癌模型评估体外肿瘤迁移和侵袭。使用 MMP9（小鼠）酶联免疫吸附测定试剂盒测量血清 MMP9 浓度。通过 Western blot 分析鉴定蛋白表达。在这项研究中，我们确定了 T0901317 和/或 EGFR-TKI 对 A549 和 HCC827-8-1 肺癌细胞系的体外和体内作用。我们证实，LXR 激动剂 T0901317 和吉非替尼的联合使用可以抑制肺癌的迁移和侵袭，无论是在体内还是体外，这种作用可能是通过抑制 ERK/MAPK 信号通路实现的。我们的研究表明，LXR 激动剂 T0901317 和吉非替尼的联合使用可以抑制肺癌的迁移和侵袭，无论是在体内还是体外。
