Chen Xuewei, Chen Yingxin, Xie Jieyu, Fu Junjun, Zhang Xin
Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.
J Thorac Dis. 2024 Nov 30;16(11):7526-7538. doi: 10.21037/jtd-24-781. Epub 2024 Nov 29.
17-hydroxy-jolkinolide B (HJB) is a natural diterpenoid compound derived from plants of the family that has anticancer properties against various types of tumors. However, its action and underlying mechanism in lung adenocarcinoma (LUAD) progression remain largely unknown. Thus, this research aimed to explore the role of HJB in LUAD pathogenesis and its clinical significance in tumor therapy.
Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and scratch wound-healing assay were utilized to evaluate the effect of HJB on proliferation, colony formation, and migration of LUAD cells . The syngeneic and xenograft tumor models were used to evaluate the anti-tumor activity of HJB in combination with cytotoxic T-lymphocyte antigen 4 antibody (CTLA4ab) on LUAD . In addition, quantitative real-time polymerase chain reaction (qPCR) and western blotting analyses were used to analyze the expression of programmed death ligand 1 (PD-L1). Lentiviral transduction and transfection were used to explore the related mechanism.
Experimental data demonstrated that HJB inhibited cell viability, colony formation, and migration of murine and human LUAD cells . The syngeneic and xenograft tumor models indicated that HJB possessed a remarkable anti-tumor activity and potentiated immune checkpoint blockades (ICBs) therapy. Moreover, PD-L1 might serve as a novel target in HJB-suppressed lung cancer.
By targeting PD-L1, HJB inhibited tumor cell proliferation and colony formation, as well as migration ability and . Besides, HJB enhanced CTLA4ab therapy and may be a potential agent for LUAD therapy.
17-羟基jolkinolide B（HJB）是一种从该科植物中提取的天然二萜类化合物，对多种类型的肿瘤具有抗癌特性。然而，其在肺腺癌（LUAD）进展中的作用及潜在机制在很大程度上仍不清楚。因此，本研究旨在探讨HJB在LUAD发病机制中的作用及其在肿瘤治疗中的临床意义。
采用细胞计数试剂盒-8（CCK-8）检测、集落形成检测和划痕伤口愈合检测来评估HJB对LUAD细胞增殖、集落形成和迁移的影响。同基因和异种移植肿瘤模型用于评估HJB联合细胞毒性T淋巴细胞抗原4抗体（CTLA4ab）对LUAD的抗肿瘤活性。此外，采用定量实时聚合酶链反应（qPCR）和蛋白质免疫印迹分析来分析程序性死亡配体1（PD-L1）的表达。利用慢病毒转导和转染来探索相关机制。
实验数据表明，HJB抑制小鼠和人LUAD细胞的活力、集落形成和迁移。同基因和异种移植肿瘤模型表明，HJB具有显著的抗肿瘤活性，并增强了免疫检查点阻断（ICB）治疗。此外，PD-L1可能是HJB抑制肺癌的一个新靶点。
通过靶向PD-L1，HJB抑制肿瘤细胞增殖、集落形成以及迁移能力。此外，HJB增强了CTLA4ab治疗效果，可能是LUAD治疗的一种潜在药物。
