title: Increased multi-drug resistance and reduced apoptosis in osteosarcoma side population cells are crucial factors for tumor recurrence.
abstract: The present study investigated the characteristic features of cancer stem cells (CSCs) using an aggressive human osteosarcoma cell line OS-65. Hoechst 33342 dye exclusion was used to distinguish the cancer stem-like side population (SP) cells from OS-65 cells. Furthermore, the SP cells were characterized via chemoresistance and cell death assays, reverse transcription-quantitative polymerase chain reaction and immunofluorescence. The present study identified ~3.3% of cancer stem-like SP cells from OS-65 cells whose prevalence is reduced significantly (0.9%) following treatment with verapamil. It was demonstrated that osteosarcoma SP cells are highly efficient at generating additional sarcospheres as transcriptional regulation of stemness genes, including SOX2, OCT-4 and NANOG, is highly upregulated. Notably, these SP cells demonstrated high resistance against chemotherapeutic drugs and apoptosis via elevated transcriptional regulation of several ATPase binding cassette (ABC) transporter and anti-apoptotic proteins, including ABCG2, ABCB1/MDR1 ABCB5, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein, respectively. The results of the present study suggested that CSCs may be a novel therapeutic target for the prevention of tumor relapse.
authors.affiliation: Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Daqing Oilfields General Hospital, Daqing, Heilongjiang 163000, P.R. China.
authors.forename: Jia-Song
authors.initials: JS
authors.lastname: Teng
keywords: ATPase binding cassette transporters; anticancer drugs; drug resistance; metastasis; sarcospheres; side population cells