title: Silencing of the TPM1 gene induces radioresistance of glioma U251 cells.
abstract: The present study was designed to investigate the relationship between tropomyosin 1 (TPM1) and radioresistance in human U251 cells. Radioresistant U251 (RR-U251) cells were established by repeated small irradiating injury. TPM1 levels in the U251 and RR-U251 cells were inhibited by transfection with TPM1-short hairpin RNA (shRNA) while overexpression was induced by treatment with pcDNA3.1‑TPM1. The radiosensitivity of the U251 and RR-U251 cells and the plasmid-transfected cells was evaluated by cell viability, migration and invasion assays. Cell apoptosis was also examined in vitro. The radiosensitivity of U251 xenografts was observed by tumor growth curve after radiotherapy in an in vivo experiment. Western blotting and immunohistochemistry were used to detect the level of TPM1 in vivo. The expression of TPM1 was significantly decreased in the RR-U251 cells, which may be correlated with the radioresistance of the glioma U251 cells. In the TPM1-silenced RR-U251 and TPM1-silenced U251 cells, cell viability, migration and invasion ability were significantly increased, and the rate of cell apoptosis was decreased. Consistent with these results, in the TPM1-overexpressing U251 and RR-U251 cells, cell viability, migration and invasion abilities were markedly decreased, and increased apoptosis was noted when compared to the control group. Tumor growth of the U251 xenografts was significantly inhibited following treatment with pcDNA3.1‑TPM1 combined with radiotherapy. Taken together, these results indicate that TPM1 may be one mechanism underlying radiation resistance, and TPM1 may be a potential target for overcoming the radiation resistance in glioma.
authors: Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Hua-Qing
authors: HQ
authors: Du
authors: Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Ying
authors: Y
authors: Wang
authors: Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Yao
authors: Y
authors: Jiang
authors: Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Chen-Han
authors: CH
authors: Wang
authors: Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Tao
authors: T
authors: Zhou
authors: Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Hong-Yi
authors: HY
authors: Liu
authors: Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Hong
authors: H
authors: Xiao
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D020868:Gene Silencing; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D014335:Tropomyosin / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: C490775:TPM1 protein, human; D014335:Tropomyosin