title: Downregulation of Src enhances the cytotoxic effect of temozolomide             through AKT in glioma.
abstract: Src is an attractive target since it is overexpressed in a number of malignancies,             including glioma. However, the mechanism of Src signaling as well as its silencing             effect on temozolomide in glioma is not well known. We hypothesized that downregulation             of Src may enhance the cytotoxic effect of temozolomide on glioma. As expected,             Src was overexpressed in glioblastoma multiforme (GBM) compared with normal brain             tissues. Src silencing suppressed tumor proliferation and induced apoptosis in             glioma. In addition, Src silencing combined with temozolomide treatment resulted             in significant inhibition of tumor growth. These effects may be mediated by AKT             which is a downstream effector of Src, since downregulation of AKT exhibited a             similar effect as Src siRNA when combined with temozolomide. Finally, we demonstrated             that overexpression of AKT suppressed the enhanced cytotoxic effect of temozolomide             mediated by Src silencing. Thus, the present study demonstrated that Src plays             a biologically significant role in tumor proliferation and apoptosis and enhances             the cytotoxic effect of temozolomide through AKT supression in glioma.
authors: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
authors: Zengguang
authors: Z
authors: Wang
authors: Jikui
authors: J
authors: Sun
authors: Xue
authors: X
authors: Li
authors: Shuyuan
authors: S
authors: Yang
authors: Shuyuan
authors: S
authors: Yue
authors: Jianning
authors: J
authors: Zhang
authors: Xuejun
authors: X
authors: Yang
authors: Tao
authors: T
authors: Zhu
authors: Rongcai
authors: R
authors: Jiang
authors: Weidong
authors: W
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: D003606:Dacarbazine; D019061:src-Family Kinases; D051058:Oncogene Protein v-akt; D000077204:Temozolomide