Gambogic acid suppresses hypoxia-induced hypoxia-inducible factor-1α/vascular endothelial growth factor expression via inhibiting phosphatidylinositol 3-kinase/Akt/mammalian target protein of rapamycin pathway in multiple myeloma cells.
Bottom Line: We found that hypoxia induced increase in the level of HIF-1α subunit protein and activated the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target protein of rapamycin (mTOR) pathway.Mechanistic studies exhibited that GA inhibited the production of HIF-1α by reducing phosphorylation of Akt and mTOR in U266 cells.Taken together, our results identify that GA suppresses hypoxia-activated pathways that are linked to MM progression, at least partly, by the inhibition of the PI3K/Akt/mTOR signaling pathway.
Affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, Zhongda Hospital, Southeast University, Nanjing, China.Show MeSH
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Mentions: Tumor xenografts transplanted by U266 cells were used to evaluate the antitumor effect of GA in BALB/c nude mice in vivo. After 14-day treatments, the tumors were moved and photographed (Fig. 5a). The average tumor size of control group was 615.5 ± 69.8 mm3 while those of GA treated groups were 323.3 ± 53.5 mm3 (2 mg/kg per 2 days) and 163.3 ± 30.1 mm3 (4 mg/kg per 2 days), respectively (Fig. 5b). The average tumor weight of the control group was 0.590 ± 0.099 g, while those of GA treated groups were 0.431 ± 0.074 g (2 mg/kg per 2 days) and 0.223 ± 0.064 g (4 mg/kg per 2 days), respectively (Fig. 5c). The results indicated that GA significantly inhibited tumor growth in a dosage-dependent manner. Moreover, administration of GA did not affect the body weight of mice (Fig. 5d), suggesting the maximal dose of GA (4 mg/kg per 2 days) is not toxic or at least a low toxicity for mice.
Affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, Zhongda Hospital, Southeast University, Nanjing, China.