title: Oncolytic adenovirus‑mediated mda‑7/IL‑24 expression suppresses osteosarcoma growth and enhances sensitivity to doxorubicin.
abstract: 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 polymerase 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.
authors.affiliation: Department of Anesthesiology, Jilin Cancer Hospital, Changchun, Jilin 130000, P.R. China.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Libo
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The Fourth Hospital of Jilin University, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Jilin University, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Jilin University, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, China‑Japan Union Hospital of Jilin University, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: Zhao
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D050130:Oncolytic Virotherapy; D012516:Osteosarcoma / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D004317:Doxorubicin; D007378:Interleukins; D009363:Neoplasm Proteins; D000099180:Interleukin-24; C116614:ABCG2 protein, human