Osteosarcoma (OS) is a malignant disease with a high mortality rate and poor response to current chemotherapy. Melanoma differentiation associated gene-7 (Mda7)/interleukin (IL)-24 has been demonstrated to suppress the growth of OS. However, the expression level of Mda7/IL-24 mediated by the current adenoviral vector is limited for effective clinical treatment of OS. In order to solve this issue, an oncolytic adenovirus was employed to express IL-24 (OA-IL-24) in OS cells. Quantitative

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... e chain reaction, immunoblot and ELISA assays verified that OA-IL-24 expressed IL-24 at a higher level than the replication-deficient adenoviral vector, Ad-IL24. OA-IL-24 infection led to decreased cell viability and increased apoptosis of OS cells, compared with Ad-IL-24. Animal studies further confirmed the increased anti-tumor activity of OA-IL-24. Notably, OA-IL-24 was also found to sensitize OS cells to doxorubicin. OA-IL-24-induced multiple drug resistance reversion was associated with reduced expression of Pgp and BCRP1, as well as minimized autophagy. Furthermore, restoring Pgp and BCRP1 expression as well as autophagy, was able to rescue the effect of IL-24 on the cytotoxicity of doxorubicin to OS. In conclusion, a method for inducing a high expression of IL-24 in OS was provided. In addition, IL-24 was demonstrated to increase the sensitivity of OS to doxorubicin. Materials and methods Cell lines and culture.