EGCG regulated osteolytic microenvironment to enhance the antitumor effect of DOX on orthotopic osteosarcoma. (July 2022)

• Record Type: Journal Article
• Authors: Hu, Dongcai; Lin, KeJiang; Gao, Xiang; Zhou, Mengxue; Geng, Huan
• Is Part Of: Journal of functional foods. Volume 94(2022)
• Publication Date: 2022-07
• Subjects: Orthotopic osteosarcoma -- Osteolysis -- EGCG -- Doxorubicin -- Chemotherapy; EGCG epigallocatechin gallate -- DOX doxorubicin -- BMMs bone marrow-derived macrophages -- M-CSF macrophage colony-stimulating factor -- RANK receptor activator of NF-κB -- RANKL Receptor activator of NF-κB ligand -- H&E hematoxylin and eosin -- AKT protein kinase B -- GAPDH glyceraldehyde-phosphate dehydrogenase -- TRAP tartrate-resistant acid phosphatase -- CDI coefficient of drug interaction -- CCK-8 cell counting kit 8 -- SDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresis -- OD optical density -- DAPI 4′, 6-diamidino-2-phenylindole -- α-MEM alpha-minimum essential medium -- MOD mean optical density -- FBS fetal bovine serum -- RIPA radioimmunoprecipitation assay -- Micro-CT micro-computed tomography -- BMD bone mineral density -- BV/TV trabecular bone volume per tissue volume -- Tb. N trabecular number -- Tb. Th trabecular thickness -- Tb. Sp trabecular separation -- EDTA ethylene diamine tetraacetic acid -- HRP horseradish peroxidase -- SPSS statistical product service solutions -- ANOVA analysis of variance -- SD standard deviation; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2022.105118
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Here, we demonstrated that EGCG could enhance the anti-osteosarcoma effect of DOX in vivo and in vitro. The combination of DOX and EGCG could inhibit the activity of osteoclasts at the tumor-bone interface, thereby preventing tumor-induced osteolysis and blocking the vicious circle. Taken together, EGCG may be used as an adjuvant chemotherapy drug to treat osteosarcoma. Highlights: EGCG enhanced DOX-induced proliferation inhibition of 143B Cells. EGCG in synergy with DOX inhibited osteoclast differentiation and bone resorption in vitro. EGCG in synergy with DOX inhibited AKT phosphorylation in 143B cells and BMMs. EGCG could enhance the anti-osteosarcoma and anti- osteolysis effect of DOX in vivo. Abstract: Osteosarcoma is the most common malignant bone tumor with the pathological essence of osteolysis. Doxorubicin (DOX) is common in adjuvant chemotherapy of osteosarcoma. However, it is required to address the conflict between enhancing its dose to improve efficacy and reducing its complications and chemotherapy resistance. Previous studies have demonstrated that EGCG has an antitumor and osteoclastogenesis inhibition effect. However, the combined effect of EGCG and DOX on osteosarcoma is still unclear. Here, EGCG was demonstrated to enhance the 143B cell proliferation inhibition and anti-osteoclastogenesis effect of DOX in vitro. The results suggest that EGCG in synergy with DOX inhibited AKT phosphorylation, which was involved in 143B cells proliferation and osteoclastogenesis. In vivo, the combination of DOX and EGCG could reduce tumor volume and osteolysis destruction compared with the DOX treatment group. This present study raised the possibility that EGCG may be used as an adjuvant chemotherapy drug to treat osteosarcoma.