Ligustilide inhibits the proliferation of non-small cell lung cancer via glycolytic metabolism.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide. The abnormal activation of glycolytic metabolism and PTEN/AKT signaling in NSCLC cells are highly correlated with their proliferation abilities and viability. Ligustilide is one of the major bioactive components of multiple Chinese traditional medicine including Angelica sinensis and Ligusticum. Ligustilide exposure inhibits the proliferation and viability of multiple cancer cell lines in vitro. However, the impact of ligustilide to the progression of NSCLC and its detailed pharmacological mechanisms remain unclear. In this research, CCK-8 and colony formation assay were performed to demonstrate ligustilide treatment inhibited the viability and proliferation ability of NSCLC cells in vitro. Caspase-3/-7 activity assay and nucleosome ELISA assay were utilized to show ligustilide promoted the apoptosis of NSCLC cells. Metabolic analysis and qRT-PCR assay were used to demonstrated that ligustilide dampened aerobic glycolysis of NSCLC cells. Nude mice were exposed to 5 mg/kg ligustilide and ligustilide inhibited orthotopic NSCLC growth in vivo. qRT-PCR and Western blot analysis were performed to substantiate the regulatory function of ligustilide to PTEN/AKT signaling in NSCLC cells. Overall, this study revealed that ligustilide regulated the proliferation, apoptosis and aerobic glycolysis of NSCLC cells through PTEN/AKT signaling pathway.

Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells.

BACKGROUND: Monoclonal antibodies targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) have been developed to treat cancers including lung cancer. In this study, we aimed to investigate whether lycopene could promote the effect of anti-PD-1 treatment on lung cancer. METHODS: Tumor formation assay was conducted. Immune reactions were assessed by detecting several cytokine levels using enzyme-like immunosorbent assay. T cell activity was analyzed using cytometry. The mechanism of lycopene action was investigated using Western blot, quantitative real-time polymerase chain reaction and bisulfite sequencing analysis. RESULTS: After the mice injected with Lewis lung carcinoma (LLC) cells were sacrificed, we found that combined lycopene and anti-PD-1 reduced the tumor volume and weight compared to control treatment. Cell apoptosis in the tumor tissues was significantly enhanced in mice with combined lycopene and anti-PD-1 treatment in comparison with those of either lycopene or anti-PD-1 alone. Furthermore, lycopene could assist anti-PD-1 to elevate the levels of interleukin (IL)-1 and interferon (IFN) γ while reduce the levels of IL-4 and IL-10 in the spleen of mice injected with LLC cells. Lycopene treatment increased the CD4+/CD8+ ratio in the spleen and promoted IFNγ-expressing CD8+ T cells in tumor tissues. Upon IFNγ stimulation, lycopene diminished PD-L1 expression via activating JAK and repressing phosphorylation of AKT. CONCLUSION: Our results have demonstrated that lycopene could be used as a potential adjuvant drug to synergistically improve the efficiency of anti-PD-1 therapy.