17-hydroxy-jolkinolide B potentiated CTLA4ab therapy through targeting tumor suppression and immune activation by downregulating PD-L1 expression in lung adenocarcinoma.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.