Overexpression Of Pleiotrophin Contributes To Doxorubicin Resistance Of Osteosarcoma

Doxorubicin(DOX)is one of the major chemotherapeutic drugs used in the treatment of human osteosarcoma(OS).However,acquisition of DOX resistance,frequently occurring in patients with OS,leads to poor survival rate of OS patients.Pleiotrophin(PTN)is a proto-oncogene overexpressed in various malignant human tumors.Studies concerning the role of PTN in OS are limited.In this study,we initially established two DOX resistant cell lines.We found that PTN expression was elevated in DOX resistant cells(HOS/DOX and MG63/DOX)compared to their parental cells;and down-regulating the PTN level by RNA interference could enhance the therapeutic efficacy of DOX to DOX resistant OS cells.In addition,PTN expression was significantly up-regulated in OS tumors compared to normal tissues;and increased PTN expression in OS was associated with inferior disease-free survival.Taken together,the results presented here suggest that PTN is a promising therapeutic target for OS treatment in future.