title: TopBP1 contributes to the chemoresistance in non-small cell lung cancer through upregulation of p53.
abstract: Resistance to chemotherapeutic drugs is a major obstacle in non-small cell lung cancer (NSCLC) therapy. The molecular determinants of NSCLC resistance to doxorubicin are unknown. In the present study, we investigated whether topoisomerase IIβ binding protein 1 (TopBP1) was involved in the chemoresistance to doxorubicin in NSCLC cancer. We found that p53-deficient lung cancer cells (NCI-H1299) displayed the greatest resistance to doxorubicin compared with NCI-H358, A549, and HCC827 cells with p53 expression. The expression of TopBP1 was significantly higher in NCI-H1299 cells than the other three tumor cell lines. In addition, TopBP1 knockdown with specific small interfering RNA in NCI-H1299 cells enhanced the doxorubicin chemosensitivity and decreased the expression of p53 in the presence of doxorubicin. After doxorubicin administration, co-immunoprecipitation assay showed that TopBP1 promoted the expression of p53 in NCI-H1299 cells. These results for the first time demonstrated that TopBP1 plays an important role in NSCLC chemoresistance via upregulation of p53. Therefore, inhibition of TopBP1, in combination with chemotherapy, may represent a novel strategy for the treatment of chemotherapy-resistant NSCLC.
authors.affiliation: Department of Oncology, Xinchang People's Hospital, Shaoxing.
authors.forename: Yinxiang
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Eye Centre, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Oncology, Xinchang People's Hospital, Shaoxing.
authors.forename: Xican
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Shufen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Xianning
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110513:TOPBP1 protein, human; D016159:Tumor Suppressor Protein p53
keywords: TopBP1; drug resistance; non-small cell lung cancer; p53