Chemoresistance is a major cause for the poor prognosis of osteosarcoma (OS) patients. However, our understanding of mechanisms underlying chemoresistance in OS are limited. The present study aimed to investigate the effect of stathmin 1 (STMN1) on paclitaxel-induced chemoresistance, as well as the underlying mechanism. Western blot analysis data revealed that the expression level of STMN1 was dramatically increased in OS cell lines (HOS, Saos-2, U-2OS and MG-63), when compared to normal osteoblast hFOB1.19 cells. Furthermore, treatment with paclitaxel led to upregulation of STMN1 in U-2OS cells, accompanied by activation of autophagy, which may attenuate the cytotoxicity of paclitaxel in OS cells. Following knockdown of STMN1 expression, paclitaxel-induced autophagy was significantly reduced, accompanied by increased cytotoxicity of paclitaxel to U-2OS cells. In addition, blockade of mammalian target of rapamycin signaling attenuated the inhibitory effect of STMN1 knockdown on autophagy in OS cells. In conclusion, the present study demonstrated that knockdown of STMN1 enhances osteosarcoma cell chemosensitivity to paclitaxel through inhibition of autophagy. Therefore, STMN1 may be a potential target for the treatment of chemoresistant OS.
Keywords: autophagy; chemoresistance; osteosarcoma; paxilitaxel; stathmin 1.