Inhibitory Effect of Noggin on Osteolytic Bone Metastasis of Breast Cancer
ZHANG Ying1*, ZHANG Zhihui2
The aim of this article was to investigate the inhibitory effect of Noggin on osteolytic bone metastasis of human breast cancer MDA-MB-231 cells as well as the possible mechanism. Noggin lentivirus was used to infect the breast cancer MDA-MB-231 cells in vitro. Western blot was used to detect the expression of Noggin in breast cancer cells. CCK8 and flow cytometry were used to detect the changes of cell proliferation and cell cycle.Western blot was used to detect the changes of BMPs/SMAD cell signal pathway, total protein and phosphorylated protein of Akt and mTOR, which were the key molecule protein of PI3K/Akt/mTOR cell signal pathway. Breast cancer cells were injected into the tibia of nude mice to build bone metastasis animal models. The effect of Noggin on osteolytic bone metastasis of breast cancer was examined by X-ray. Immunohistochemistry was used to detect the changes of PCNA, total and phosphorylated Akt protein in bone metastasis tissues of breast cancer. The expression of Noggin protein was significantly increased in Noggin group. The CCK8 showed that the absorbance of Noggin lentivirus group was (0.452±0.059) significantly lower than the RFP group (0.683±0.064) after the third day of Noggin lentivirus infected cells. Western blot showed that the total protein of Akt and mTOR was unchanged but the phosphorylated protein expression was significantly decreased. The osteolytic bone defect of Noggin group was significantly lower than RFP group. Immunohistochemistry showed that PI3K/Akt/mTOR was involved in osteolytic bone metastasis. The expression of phosphorylated Akt and PCNA were decreased significantly. Noggin may inhibit the osteolytic bone metastasis of breast cancer by inhibiting the PI3K/Akt/mTOR pathway in vivo and in vitro.
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