Silencing of Barkor/ATG14 sensitizes osteosarcoma cells to cisplatin‑induced apoptosis

Zhao,Zhifang; Tao,Lijiang; Shen,Chengchun; Liu,Bing; Yang,Zhengming; Tao,Huimin

doi:10.3892/ijmm.2013.1578

2014-February Volume 33 Issue 2

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2014-February Volume 33 Issue 2

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Article Open Access

Silencing of Barkor/ATG14 sensitizes osteosarcoma cells to cisplatin‑induced apoptosis

Authors:
- Zhifang Zhao
- Lijiang Tao
- Chengchun Shen
- Bing Liu
- Zhengming Yang
- Huimin Tao
View Affiliations / Copyright

Affiliations: Department of Orthopedic Surgery, The 117th Hospital of People's Liberation Army, Hangzhou, Zhejiang, P.R. China, Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China

Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 271-276
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Published online on: December 9, 2013

https://doi.org/10.3892/ijmm.2013.1578
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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 reticulum (ER) stress-associated apoptosis. Bcl-2 was markedly downregulated in dose‑dependent cisplatin‑treated Barkor-transfected-Saos-2 cells. Findings of the present study suggest that the combination of silencing of Barkor and cisplatin enhanced the antitumor efficacy through the Barkor‑related ER- and mitochondrial-mediated apoptotic pathway.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Silencing of Barkor/ATG14 sensitizes osteosarcoma cells to cisplatin‑induced apoptosis

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