Department of Orthopedics, The First Affiliated Hospital of Henan University, Kaifeng 475001, China.
Department of Orthopedics, The First Affiliated Hospital of Henan University, Kaifeng 475001, China.
Chem Biol Interact. 2018 Jun 25;290:44-51. doi: 10.1016/j.cbi.2018.05.007. Epub 2018 May 18.
Osteosarcoma (OS) is the most common bone malignancy in children and adolescents. Combined treatments of anti-cancer drugs can remarkably improve chemotherapeutic outcomes. Gemcitabine and licoricidin both have potential anti-tumor activity in several cancers. However, the combined therapeutic efficiency of gemcitabine and licoricidin for OS has not been explored. Here, we found that licoricidin or gemcitabine inhibited OS cell viability in a dose-dependent manner. Cotreatment with licoricidin and gemcitabine enhanced gemcitabine-induced cytotoxicity in OS cells. Licoricidin suppressed activation of the Akt and nuclear factor-kappa B (NF-κB) pathways. Gemcitabine had no effect on Akt signal, but facilitated the activation of NF-κB signal in OS cells. Moreover, combined treatment of licoricidin and gemcitabine markedly curbed the activation of Akt and NF-κB pathways in OS cells. Inhibition of the Akt and NF-κB pathways enhanced gemcitabine-induced cytotoxicity in OS cells. In vivo assay further manifested that licoricidin enhanced gemcitabine-induced cytotoxicity in tumor xenograft models of OS via inactivation of the Akt and NF-κB pathways. In conclusion, licoricidin enhanced gemcitabine-induced cytotoxicity in OS cells by inactivation of the Akt and NF-κB pathways in vitro and in vivo.
骨肉瘤（OS）是儿童和青少年中最常见的骨恶性肿瘤。抗癌药物的联合治疗可以显著改善化疗效果。吉西他滨和甘草素在几种癌症中都具有潜在的抗肿瘤活性。然而，吉西他滨和甘草素联合治疗骨肉瘤的疗效尚未得到探索。在这里，我们发现甘草素或吉西他滨以剂量依赖性方式抑制 OS 细胞活力。甘草素和吉西他滨联合治疗增强了吉西他滨诱导的 OS 细胞毒性。甘草素抑制 Akt 和核因子-κB（NF-κB）通路的激活。吉西他滨对 Akt 信号没有影响，但促进了 NF-κB 信号在 OS 细胞中的激活。此外，甘草素和吉西他滨联合治疗显著抑制了 OS 细胞中 Akt 和 NF-κB 通路的激活。抑制 Akt 和 NF-κB 通路增强了 OS 细胞中吉西他滨诱导的细胞毒性。体内实验进一步表明，甘草素通过抑制 Akt 和 NF-κB 通路增强了吉西他滨在骨肉瘤肿瘤异种移植模型中的细胞毒性。总之，甘草素通过体外和体内抑制 Akt 和 NF-κB 通路增强了吉西他滨诱导的 OS 细胞毒性。
