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• Zhang, G
• Li, M
• Zhu, X
• Bai, Y
• Yang, C
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• Li, M
• Zhu, X
• Bai, Y
• Yang, C
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• Li, M
• Zhu, X
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• Yang, C

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Int. J. Mol. Sci. 2011, 12(5), 2994-3005; doi:10.3390/ijms12052994

Article

Knockdown of Akt Sensitizes Osteosarcoma Cells to Apoptosis Induced by Cisplatin Treatment

Guoyou Zhang ^†, Ming Li ^†,* , Xiaodong Zhu, Yushu Bai and Changwei Yang

Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China ^† These authors contributed equally to this work.

* Author to whom correspondence should be addressed.

Received: 9 March 2011; in revised form: 15 April 2011 / Accepted: 18 April 2011 / Published: 10 May 2011

(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)

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Abstract: Akt plays an important role in the inhibition of apoptosis induced by chemotherapy and other stimuli. We therefore investigated if knockdown of Akt2 promoted drug-induced apoptosis in cultured osteosarcoma cells in vitro. SAOS-2 cells were transfected with Akt2 siRNA. The sensitivity of the transformed cell line to the chemotherapeutic drug cisplatin was assessed. Reduced expression of Akt2 did not directly inhibit the growth rate of the transfected cells; however, it significantly increased their sensitivity to cisplatin. Knockdown of Akt2, together with cisplatin treatment, promoted the expression of p53 up-regulated modulator of apoptosis (PUMA). It is possible that the augmentation of cisplatin cytotoxicity may be mediated by PUMA activation. The results of this study suggest that knockdown of Akt2 expression may have therapeutic applications in enhancing the efficacy of chemotherapy in patients with osteosarcoma.

Keywords: osteosarcoma; Akt; PUMA; apoptosis; cisplatin; chemotherapy

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