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Knockdown of Akt sensitizes osteosarcoma cells to apoptosis induced by cisplatin treatment.

Zhang G, Li M, Zhu X, Bai Y, Yang C - Int J Mol Sci (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; E-Mails: Zhangguoyou7@gmail.com (G.Z.); zhgych@yahoo.com.cn (X.Z.); baiyushu@21cn.com (Y.B.); changwei_y@yahoo.com.cn (W.Y.).

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.

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Related in: MedlinePlus

Knockdown of Akt2 combined with cisplatin treatment upregulates PUMA. Western blot analysis of PUMA in untransfected, Akt2-siRNA-transfected, and Akt-3m-siRNA-transfected SAOS-2 cells treated with cisplatin (10 μM) for 2–6 h. A rapid increase in PUMA levels occurred in Akt2-siRNA-transfected SAOS-2 treated with cisplatin.
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f6-ijms-12-02994: Knockdown of Akt2 combined with cisplatin treatment upregulates PUMA. Western blot analysis of PUMA in untransfected, Akt2-siRNA-transfected, and Akt-3m-siRNA-transfected SAOS-2 cells treated with cisplatin (10 μM) for 2–6 h. A rapid increase in PUMA levels occurred in Akt2-siRNA-transfected SAOS-2 treated with cisplatin.

Mentions: Chemotherapeutic agents have previously been found to activate PUMA [9]. In the present study, treatment of Akt2-siRNA-transfected SAOS-2 with cisplatin (10 μM) for 2–6 h induced a rapid increase in PUMA levels (Figure 6). These findings suggest that sensitization of cells by Akt2 silencing proceeds via PUMA activation.


Knockdown of Akt sensitizes osteosarcoma cells to apoptosis induced by cisplatin treatment.

Zhang G, Li M, Zhu X, Bai Y, Yang C - Int J Mol Sci (2011)

Knockdown of Akt2 combined with cisplatin treatment upregulates PUMA. Western blot analysis of PUMA in untransfected, Akt2-siRNA-transfected, and Akt-3m-siRNA-transfected SAOS-2 cells treated with cisplatin (10 μM) for 2–6 h. A rapid increase in PUMA levels occurred in Akt2-siRNA-transfected SAOS-2 treated with cisplatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3116170&req=5

f6-ijms-12-02994: Knockdown of Akt2 combined with cisplatin treatment upregulates PUMA. Western blot analysis of PUMA in untransfected, Akt2-siRNA-transfected, and Akt-3m-siRNA-transfected SAOS-2 cells treated with cisplatin (10 μM) for 2–6 h. A rapid increase in PUMA levels occurred in Akt2-siRNA-transfected SAOS-2 treated with cisplatin.
Mentions: Chemotherapeutic agents have previously been found to activate PUMA [9]. In the present study, treatment of Akt2-siRNA-transfected SAOS-2 with cisplatin (10 μM) for 2–6 h induced a rapid increase in PUMA levels (Figure 6). These findings suggest that sensitization of cells by Akt2 silencing proceeds via PUMA activation.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; E-Mails: Zhangguoyou7@gmail.com (G.Z.); zhgych@yahoo.com.cn (X.Z.); baiyushu@21cn.com (Y.B.); changwei_y@yahoo.com.cn (W.Y.).

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.

Show MeSH
Related in: MedlinePlus