B7-H3 promotes colorectal cancer angiogenesis through activating the NF-kappa B pathway to induce VEGFA expression
CELL DEATH & DISEASE
Authors: Wang, Ruoqin; Ma, Yanchao; Zhan, Shenghua; Zhang, Guangbo; Cao, Lei; Zhang, Xueguang; Shi, Tongguo; Chen, Weichang
Abstract
Tumor angiogenesis is a hallmark of cancer and is involved in the tumorigenesis of solid tumors. B7-H3, an immune checkpoint molecule, plays critical roles in proliferation, metastasis and tumorigenesis in diverse tumors; however, little is known about the biological functions and molecular mechanism underlying B7-H3 in regulating colorectal cancer (CRC) angiogenesis. In this study, we first demonstrated that the expression of B7-H3 was significantly upregulated and was positively associated with platelet endothelial cell adhesion molecule-1 (CD31) level in tissue samples from patients with CRC. In addition, a series of in vitro and in vivo experiments showed that conditioned medium from B7-H3 knockdown CRC cells significantly inhibited the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs), whereas overexpression of B7-H3 had the opposite effect. Furthermore, B7-H3 promoted tumor angiogenesis by upregulating VEGFA expression. Recombinant VEGFA abolished the inhibitory effects of conditioned medium from shB7H3 CRC cells on HUVEC angiogenesis, while VEGFA siRNA or a VEGFA-neutralizing antibody reversed the effects of conditioned medium from B7-H3-overexpressing CRC cells on HUVEC angiogenesis. Moreover, we verified that B7-H3 upregulated VEGFA expression and angiogenesis by activating the NF-kappa B pathway. Collectively, our findings identify the B7-H3/NF-kappa B/VEGFA axis in promoting CRC angiogenesis, which serves as a promising approach for CRC treatment.
In Silico Decipherment of Corydalis yanhusuo Mode of Action in the Femoral Head Osteonecrosis
LATIN AMERICAN JOURNAL OF PHARMACY
Authors: Zhao, Wubin; Lin, Kuiran; Zu, Zhanjie; Anam, Hafsa; Asad, Mhhb; Murtaza, Ghulam
Abstract
Osteonecrosis of the femoral head is a disabling disease, which usually leads to destructive osteoarthritis of the hip joint. The mechanism of action of the herbal medicines is essentially explored to find out their efficacy. Corydalis yanhusuo is a traditional Chinese medicine (TCM) and is traditionally been used for the treatment of femoral head osteonecrosis, nonetheless, its mode of action is still unknown. In this study, we used the TCM approach to elaborate on the mode of activity of C. yanhusuo for the treatment of femoral head osteonecrosis. A database containing active ingredients of C. yanhusuo was developed, followed by the recognition of the targets related to femoral head osteonecrosis. The relationship among these target proteins was characterized by developing and evaluating the protein-protein interaction network using GO (gene ontology) enrichment analysis using the ClueGO plugin and STITCH analysis. C. yanhusuo contained 77 chemical constituents that were having 1549 protein targets. The previous literature and experimental study documented the fact that C. yanhusuo could be used in the treatment of FHO. As a result, 28 of 1549 targets of C. yanhusuo showed pharmacological activity against FHO. While 20 out of 28 protein targets belonged to Homo sapiens. The important protein targets were VEGFA, IL6R, SRC, MMP2, and IL6R, which contribute to the functioning of C. yanhusuo. Based on the results, C. yanhusuo could be applied for the treatment of FHO. ILs effect in the treatment of femoral head osteonecrosis depends on a variety of mechanisms of action, including intracellular estrogen receptor signaling pathway, receptor tyrosine-protein kinase erbB-2 signaling pathway, and regulation of phagocytosis.