Antisense c-myc sensitizes osteosarcoma cells to cisplatin-induced apoptosis / 中国病理生理杂志

ABSTRACT

AIM: To down-regulate expression of c-myc through antisense therapy and to investigate its effect on the sensitivity of osteosarcoma MG-63 cells to cisplatin-induced apoptosis. METHODS: The recombinant adenovirus (Ad-Asc-myc) encoding antisense c-myc fragment was constructed and transfected into osteosarcoma MG-63 cells in vitro in order to down-regulate the expression of c-myc, and the change in the sensitivity to cisplatin-induced apoptosis was observed. MTT, Western blot, RT-PCR, flow cytometry (FCM) and electron microscope were used to evaluate tumor cell proliferation in vitro, genes expression related to apoptosis regulation and effects on the sensitivity of osteosarcoma MG-63 cells to cisplatin-induced apoptosis. RESULTS: Ad-Asc-myc down-regulated the expression of c-myc protein after transfected MG-63 cells for 48 h, combined with the treatment of 2.0 mg/L cisplatin for 2 h inhibited tumor cell proliferation in vitro by 38.0%. RT-PCR revealed that Ad-Asc-myc down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. No appreciable change was observed in the expression of E_2F-1. FCM showed that Ad-Asc-myc induced apoptosis in intransfected cells, and rendered it more sensitive to cisplatin. CONCLUSION: Antisense c-myc is able per se to induce apoptosis and sensitize osteosarcoma cells to cisplatin-induced apoptosis.