Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin.

Abstract

X-chromosome-linked inhibitor of apoptosis protein (XIAP) is an important member of the inhibitors of apoptosis (IAP) family. It has been shown that XIAP promotes the invasion, metastasis, growth and survival of malignant cells, and confers resistance to some chemotherapeutic drugs in various types of cancer. However, little is known regarding its detailed role in osteosarcoma (OS). In the present study, we first investigated the expression of XIAP in OS tissues, and an increased expression of XIAP in OS tissues compared to adjacent non-tumor tissue was identified. Additionally, its expression level correlated with key pathological characteristics including clinical stage, tumor size and metastasis. Subsequently, small interfering RNA (siRNA) was used to block XIAP expression to evaluate the effect of XIAP siRNA on cell proliferation, colony formation, cell cycle, apoptosis, tumorigenicity, and the combined effects of doxorubicin or cisplatin in OS cell lines (MG63 cells). Downregulation of XIAP expression using the RNA silencing approach efficiently decreased cell proliferation and colony formation, and induced cell apoptosis and cell cycle in the G0/G1 stage. In addition, this downregulation inhibited tumor growth in a nude murine model. The resuls also showed that treatment with XIAP-shRNA in combination with doxorubicin or cisplatin enhanced chemosensitivity. These results suggested that XIAP may aid the diagnosis of OS and may be an effective strategy for gene therapy of this disease.