Abstract
Although surgical excision following neoadjuvant chemotherapy has contributed to the long-term survival of osteosarcoma patients, patients that do not respond to commonly used drugs including cisplatin, have a poor prognosis. Autophagy is important in the inhibition of chemotherapeutic apoptosis. Therefore, we investigated whether knockdown of Beclin1-associated autophagy-related key regulator (Barkor/ATG14) promoted cisplatin-induced apoptosis in a drug-resistant osteosarcoma cell line in vitro. Saos-2 cells were transfected with Barkor siRNA. Sensitivity of the Barkor siRNA-transfected cell line to cisplatin was evaluated. Silencing of Barkor did not directly inhibit the growth rate of the transfected cells, but it significantly increased their sensitivity to cisplatin. The results of flow cytometry and 4',6-diamidino-2-phenylindole (DAPI) staining revealed that Barkor siRNA-transfected Saos-2 cells treated with cisplatin exhibited much higher rates of apoptosis than the control and control siRNA-transfected cells. Additionally, the combination of silencing of Barkor with cisplatin treatment promoted the expression of caspase-12 and calpain. The increase of cisplatin cytotoxicity may therefore be involved in endoplasmic retic...Continue Reading
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