title: Adenovirus-mediated coexpression of DCX and SPARC radiosensitizes human malignant glioma cells.
abstract: This study is designed to examine the radiosensitizing effects of coexpression of doublecortin (DCX) and secreted protein and rich in cysteine (SPARC). Previously, we showed that downregulation of SPARC by small interfering RNA increased radioresistance of U-87MG glioma cells. Therefore, overexpression of SPARC might increase radiosensitivity of glioma cells. But SPARC has been shown to promote glioma cell invasion both in vitro and vivo. In order to radiosensitize glioma cells without stimulating invasion, we chose DCX, which is a well-characterized anti-tumor gene, to coexpress with SPARC. An adenovirus-mediated double gene expression system was constructed and applied to U251 and A172 glioma cell lines. Our data showed that coexpression of DCX and SPARC collaboratively diminished radioresistance of glioma cells, interfered with cell cycle turnover and increased irradiation-induced apoptosis. In addition, transwell assay revealed that coexpression was able to counteract the invasion-promoting effects of SPARC, and even inhibited intrinsic invasion, evidenced by less invading cells in double gene overexpressed group than that of control adenovirus-treated group. In conclusion, genetic engineering combining two or more genes might be a more effective method to overcome radioresistance of glioma cells.
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Soochow University, No. 199 Ren'ai Street, Suzhou, 215123, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.forename: Jiahua
authors.initials: J
authors.lastname: Yu
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yang
authors.forename: Haowen
authors.initials: H
authors.lastname: Zhang
authors.forename: Guomei
authors.initials: G
authors.lastname: Tai
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Yuan
authors.forename: Fenju
authors.initials: F
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009479:Neuropeptides / Q000378:metabolism*; D015676:Osteonectin / Q000378:metabolism*; D011836:Radiation Tolerance / Q000528:radiation effects; D011995:Recombination, Genetic / Q000235:genetics; D014965:X-Rays
chemical_list: C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D015676:Osteonectin