Bone morphogenetic protein 9 facilitates osteocarcinoma cell apoptosis and inhibits in vivo tumor growth

Abstract

ABSTRACT. Osteosarcoma (OS) causes millions of death worldwide and, since there is no effective therapy, it is necessary to identify the molecular mechanism of OS, which can direct the development of new therapies. This study investigated the role of bone morphogenetic protein 9 (BMP9), a member of the transforming growth factor (TGF)-β family, in OS development. This study first examined BMP9 expression in tissue from OS patients and normal subjects. The OS cell line (MG63) and tumor cells from OS patients were then transfected with BMP9 and cell proliferation and apoptosis were assessed. Western blot and reverse transcription-polymerase chain reaction were used to study the expression of cancer-related genes [B cell lymphoma (Bcl)-2, cleaved Caspase-3, Caspase-9, and poly ADP-ribose polymerase]. To confirm the in vivo impact of BMP9, mice were transplanted with OS tumor cells and then treated with BMP9 carried in attenuated Salmonella enterica serovar Typhimurium. Our study found that the OS tumor tissue had a lower expression of BMP9 compared to normal tissue. Transfection of BMP9 in OS and MG63 cells inhibited cell growth and promoted apoptosis. In vitro studies showed a decrease in Bcl-2 gene expression and an increase in Cyto-c, Caspase-3, and Caspase-9 expression. In vivo studies indicated that consistent treatment with BMP9 in OS mice results in inhibition of tumor growth. This study shows that BMP9 inhibition is associated with OS development and that enhanced expression of BMP9 may be a potential treatment method for OS.

RETRACTED ARTICLE: TGF-β is associated with poor prognosis and promotes osteosarcoma progression via PI3K/Akt pathway activation

“…We found that si-TGF-β treatment significantly decreased the viability of U2OS/MG-63 cells (P < 0.05; Figure 2(a-c)). TGF-β has been shown to play a role in modulating osteosarcoma cell apoptosis [36]. Our results show that TGF-β downregulation directly induces an increase in S-phase cell cycle arrest and upregulates the expression of apoptosis-related markers.…”

pH-Responsive Pluronic F127–Lenvatinib-Encapsulated Halogenated Boron-Dipyrromethene Nanoparticles for Combined Photodynamic Therapy and Chemotherapy of Liver Cancer

“…Next, we explored the upstream key apoptosis-related protein–cysteine aspartate-specific protease (caspase-9). , Hep3B cells incubated with BDPBr 2 hardly expressed caspase-9 protein under light conditions, but when incubated with LBBr 2 NPs under light conditions, the expression of caspase-9 increased significantly. There was no significant difference in the expression of caspase-9 between free lenvatinib and LBBr 2 NPs without illumination.…”

LncRNA ITGB2-AS1 Could Promote the Migration and Invasion of Breast Cancer Cells through Up-Regulating ITGB2

“…It has been confirmed that BMP9, a potent osteogenetic factor, plays various roles in cancers. For example, BMP9 can inhibit the growth of lung adenocarcinoma [ 11 ], colon cancer [ 12 ], and osteocarcinoma [ 13 ], but exert a promotion effect on the proliferation and migration of liver cancer cell [ 14 ]. Additionally, in our previous research, we have found that BMP9 can inhibit the proliferation and migration of the breast cancer cell lines MDA-MB-231 [ 15 ] and SK-BR-3 [ 16 ].…”