As the most frequent cause of
cancer-related death worldwide,
lung cancer is closely related to
inflammation. The interaction between
tumor cells and inflammatory cells promotes
tumor development and
metastasis. During
tumor development, vascular endothelial cells form the most important barrier to prevent
tumor cell migration to the blood and tissue. Increased vascular permeability provides favorable conditions for the migration of
tumor cells, and endothelial tight junctions are an important component of the vascular barrier.
Protein kinase C δ is involved in the occurrence of
non-small cell lung cancer and regulates vascular permeability and
tight junction protein expression.
Src kinase was reported to play an important role in TNF-α-induced endothelial
inflammation. Ophiopogon
Saponin C1 is a new chemical compound isolated from Liriope muscari, but its pharmacological activities have not been fully elucidated. Therefore, we tested the protective effects of C1 on endothelial permeability in a model of TNF-α-induced endothelial
inflammation by transendothelial electrical resistance and
sodium fluorescein assays and verified these results in a nude mouse model of experimental pulmonary
adenocarcinoma metastasis. We further elucidated the mechanism of C1, which was based on the PKCδ and Src
proteins, by Western blotting. C1 can inhibit
lung cancer in vivo, regulate the level of plasma
inflammation in
tumor-bearing mice, and protect the pulmonary vascular barrier against injury induced by
cancer. It was investigated the expression and distribution of the TJ index
protein ZO-1 in mouse vascular endothelium and HUVECs and found that C1 could inhibit the degradation and breakage of the ZO-1
protein. Related signaling experiments confirmed that C1 can inhibit TNF-α and activation of PKCδ and
Src kinase. This study laid the foundation for further analysis of new drugs with clear mechanisms and independent intellectual property rights of traditional Chinese medicines.