Chloroquine suppresses proliferation and invasion and induces apoptosis of osteosarcoma cells associated with inhibition of phosphorylation of STAT3

Background: Osteosarcoma (OS) is characterized by a high rate of metastasis. It has been found that tumor cells can bypass apoptosis which leads to an uncontrolled proliferation, but chloroquine (CQ) can have an effect on the tumors by inducing apoptosis. We aimed to explore the effects and the hypothetical mechanism of CQ effects on OS. Methods: We first estimated the CQ effects on proliferation, apoptosis, migration, invasion, and lamellipodia formation of OS cells. Mice bearing xenograft model were used to test the anti-tumor growth and lung metastasis effects of CQ in OS. Western blot and immunohistochemistry were used to explore the mechanism of CQ effects and the association between p-STAT3 expression and lung metastasis of OS patients. Results: CQ induces the apoptosis and suppressed the viability, proliferation, migration, invasion, and lamellipodia formation of OS cells in vitro. In vivo experiments demonstrated that CQ inhibited tumor growth and lung metastasis. CQ induced apoptosis was dependent on the lysosomal inhibition and inhibition of protein turnover. The lung metastasis was associated with the p-STAT3 expression in OS patients. Conclusion: CQ inhibited progression of OS cells in vitro, and suppressed tumor growth and lung metastasis in vivo. p-STAT3 can be a predictive biomarker for lung metastasis in osteosarcoma patients.