title: Knockdown of Akt sensitizes osteosarcoma cells to apoptosis induced by cisplatin treatment.
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.
authors.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.).
authors.forename: Guoyou
authors.initials: G
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.forename: Yushu
authors.initials: Y
authors.lastname: Bai
authors.forename: Changwei
authors.initials: C
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D055785:Gene Knockdown Techniques; D006801:Humans; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin