Dipalmitoylphosphatidic acid reduces osteosarcoma growth by activation of AKT signaling pathway

作者：Liu, Wei; Wang, Shuo; Zhang, Ying-Jian; Fang, Guang-Wen; Xue, Yuan^*

来源：International Journal of Clinical and Experimental Medicine, 2018, 11(2): 627-633.

• DPPA
• osteosarcoma
• AKT

Aim: Osteosarcoma is one of the most common bone tumors. It has high malignant degree and tends to occur in adolescents. In this study, we aim to investigate the effects of dipalmitoylphosphatidic acid (DPPA) in osteosarcoma and its underlying mechanism. Methods: BALB/c mice were used for the establishment of osteosarcoma model and the KRIB cell line was purchase from America ATCC. 2x10(5) KRIB cells (10 mu l) were injected to tibias of BALB/c mice. The osteosarcoma models were successfully established after 8 weeks. When the mice grew up to 12 weeks, the treatment group were injected intraperitoneally with DPPA. While the control group were injected intraperitoneally with saline. Detection of the histological sections to make sure the establishment of osteosarcoma models. The mice in treatment and control groups were harvested and tissue samples were taken. The histological changes were detected by Hematoxylin and Eosin Staining (H&E staining); the expression of fibronectin was detected by immunohistochemistry and western blot was applied to determine the changes in (serine/threonine kinase) AKT related pathway. The variation of cell cycles and apoptosis were detected by Flow cytometric assays. Results: The osteosarcoma models were successfully established in 48 mice which were separated into two groups: the treatment and control group. The two groups were treated with DPPA and saline respectively. The histological sections demonstrated severe tissue erosion and increased infiltration of inflammatory cells in the control group, however, the inflammatory cells were significantly reduced in the treatment group with DPPA. In addition, compared to the control group with increased expression of fibronectin, decreased expression of fibronectin was detected by immunohistochemistry in the treatment group (p<0.01 compared with the control group). Flow cytometric assays showed that DPPA arrested KRIB cells at the G1 phase and increased the cell number of apoptosis (p<0.05 compared with the control group). And western blot results exhibited a higher p-AKT expression in the treatment group (p<0.001 compared with the control group). Furthermore, there was an increased survival rate after DPPA treatment. Conclusion: DPPA reduces osteosarcoma growth by activation of AKT signaling pathway.

• 出版日期2018
• 单位天津医科大学; 天津市宝坻区人民医院