Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells

被引:43
|
作者
Rugamba, Alexis [1 ]
Kang, Dong Young [1 ]
Sp, Nipin [1 ]
Jo, Eun Seong [2 ]
Lee, Jin-Moo [2 ]
Bae, Se Won [3 ]
Jang, Kyoung-Jin [1 ]
机构
[1] Konkuk Univ, Sch Med, Inst Biomed Sci & Technol, Dept Pathol, Chungju 27478, South Korea
[2] Natl Inst Food & Drug Safety Evaluat, Pharmacol Res Div, Osong Hlth Technol Adm Complex, Cheongju 28159, South Korea
[3] Jeju Natl Univ, Dept Chem & Cosmet, Jeju 63243, South Korea
基金
新加坡国家研究基金会;
关键词
silibinin; EGFR; JAK2; STAT5b; PI3K; AKT; MMP2; PD-L1; NSCLC; tumorsphere; STEM-LIKE CELLS; MATRIX METALLOPROTEINASES; METASTASIS; PATHWAY; CARCINOMA; APOPTOSIS; PI3K/AKT; INVASION; ANGIOGENESIS; MIGRATION;
D O I
10.3390/cells10071632
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This study demonstrated the molecular signaling behind the anticancer activity of silibinin in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed for molecular signaling analysis. Wound healing assay, invasion assay, and in vitro angiogenesis were performed for the anticancer activity of silibinin. The results indicated that silibinin inhibited A549, H292, and H460 cell proliferation in a concentration-dependent manner, as confirmed by the induction of G0/G1 cell cycle arrest and apoptosis and the inhibition of tumor angiogenesis, migration, and invasion. This study also assessed the role of silibinin in suppressing tumorsphere formation using the tumorsphere formation assay. By binding to the epidermal growth factor receptor (EGFR), silibinin downregulated phosphorylated EGFR expression, which then inhibited its downstream targets, the JAK2/STAT5 and PI3K/AKT pathways, and thereby reduced matrix metalloproteinase, PD-L1, and vascular endothelial growth factor expression. Binding analysis demonstrated that STAT5 binds to the PD-L1 promoter region in the nucleus and silibinin inhibited the STAT5/PD-L1 complex. Altogether, silibinin could be considered as a candidate for tumor immunotherapy and cancer stem cell-targeted therapy.
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页数:16
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