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  • Antitumor Effects of Ursolic Acid through Mediating the Inhibition of STAT3/PD-L1 Signaling in Non-Small Cell Lung Cancer Cells.

Antitumor Effects of Ursolic Acid through Mediating the Inhibition of STAT3/PD-L1 Signaling in Non-Small Cell Lung Cancer Cells.

Biomedicines (2021-04-04)
Dong Young Kang, Nipin Sp, Jin-Moo Lee, Kyoung-Jin Jang
ABSTRACT

Targeted therapy based on natural compounds is one of the best approaches against non-small cell lung cancer. Ursolic acid (UA), a pentacyclic triterpenoid derived from medicinal herbs, has anticancer activity. Studies on the molecular mechanism underlying UA's anticancer activity are ongoing. Here, we demonstrated UA's anticancer activity and the underlying signaling mechanisms. We used Western blotting and real-time quantitative polymerase chain reaction for molecular signaling analysis. We also used in vitro angiogenesis, wound healing, and invasion assays to study UA's anticancer activity. In addition, we used tumorsphere formation and chromatin immunoprecipitation assays for binding studies. The results showed that UA inhibited the proliferation of A549 and H460 cells in a concentration-dependent manner. UA exerted anticancer effects by inducing G0/G1 cell cycle arrest and apoptosis. It also inhibited tumor angiogenesis, migration, invasion, and tumorsphere formation. The molecular mechanism underlying UA activity involves UA's binding to epidermal growth factor receptor (EGFR), reducing the level of phospho-EGFR, and thus inhibiting the downstream JAK2/STAT3 pathway. Furthermore, UA reduced the expressions of vascular endothelial growth factor (VEGF), metalloproteinases (MMPs) and programmed death ligand-1 (PD-L1), as well as the formation of STAT3/MMP2 and STAT3/PD-L1 complexes. Altogether, UA exhibits anticancer activities by inhibiting MMP2 and PD-L1 expression through EGFR/JAK2/STAT3 signaling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Oct-4 Antibody, clone 9B7, clone 9B7, from mouse
Millipore
RIPA Lysis Buffer, 10X, 100 mL RIPA Lysis Buffer, 10X for Immunoprecipitation & Western Blotting.
Sigma-Aldrich
MISSION® esiRNA, targeting human STAT3
Sigma-Aldrich
Ursolic acid, ≥90%
Sigma-Aldrich
Anti-NANOG Antibody, clone 7F7.1, clone 7F7.1, from mouse
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Anti-MMP-3 Antibody, NT, from rabbit, purified by affinity chromatography