title: Knockdown of cancerous inhibitor of protein phosphatase 2A may sensitize NSCLC cells to cisplatin.
abstract: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that can stabilize some proteins by inhibiting degradation mediated by protein phosphatase 2A (PP2A) and it increases the proliferation of several cancer cells. Recent studies have highlighted a potential role for CIP2A in promoting tumor progression and metastasis. However, whether CIP2A could increase chemoresistance of cancer cells to chemotherapeutic agent cisplatin remains unclear. To determine whether CIP2A serves as a potential therapeutic target of human non-small-cell lung cancer (NSCLC), we utilized small interference RNA (siRNA) to knock down CIP2A expression in human NSCLC cells and analyzed their phenotypic changes. The data demonstrated that CIP2A silencing led to decreased proliferation, impaired clonogenicity and enhanced chemosensitivity and apoptosis to cisplatin in human NSCLC cells, as well as reduced Akt phosphorylation. In addition, overexpression of CIP2A diminished NSCLC cell chemosensitivity to cisplatin by inducing activation of Akt pathway, suggesting critical roles of CIP2A in NSCLC cell chemoresistance to cisplatin and rasing the possibility of CIP2A inhibition as a promising approach for lung cancer therapy.
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: L
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: W
authors.initials: W
authors.lastname: Qu
authors.affiliation: Department of Pathology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: L
authors.initials: L
authors.lastname: Lv
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: L
authors.initials: L
authors.lastname: Xie
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: X
authors.initials: X
authors.lastname: Song
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001324:Autoantigens / Q000235:genetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin