Lentivirus-mediated RNA interference of clusterin enhances the chemosensitivity of EJ bladder cancer cells to epirubicin in vitro
| Autor: | Jia Zheng Cao, Jun Hang Luo, Rong Hai Wu, Wei Chen, Jian Pang, Zhu Ting Tong, Jian Lu, Dan Xie |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Cell Survival Genetic Vectors Biochemistry Small hairpin RNA Cell Movement Cell Line Tumor Genetics medicine Humans Viability assay RNA Small Interfering Molecular Biology Epirubicin Antibiotics Antineoplastic Bladder cancer Clusterin biology Lentivirus Cancer Cell cycle medicine.disease G1 Phase Cell Cycle Checkpoints Molecular biology Urinary Bladder Neoplasms Oncology Drug Resistance Neoplasm Cancer cell biology.protein Molecular Medicine RNA Interference Corrigendum medicine.drug |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Clusterin (CLU) is a glycoprotein that is over-expressed in a number of malignant tumors and has been proven to correlate closely with the chemoresistance of several cancer cells to chemotherapeutic agents. However, the effect of CLU expression on the chemoresistance of bladder cancer to epirubicin remains unknown. In the present study, we aimed to elucidate the role of CLU in the chemoresistance of bladder cancer cells to epirubicin. Lentivirus-mediated RNA interference was applied to knock down CLU in EJ bladder cancer cells. The efficiency was examined by RT-PCR and western blot analysis. After stable CLU silencing, an EJ cell line was established and cells were treated with or without epirubicin. Cell viability, migration, invasiveness, clone formation and cell cycle progression were assessed by MTT assay, wound healing assay, Matrigel invasion assay, plate clone formation assay and flow cytometry, respectively. The results indicated that lentivirus-mediated RNA interference effectively silenced CLU at the RNA and protein levels. CLU knockdown increased the cytotoxicity of epirubicin to EJ bladder cancer cells. Combined treatment with lentivirus-mediated shRNA targeting CLU and epirubicin had maximum effects in bladder cancer cells on cell viability, migration, invasiveness and clone-forming ability. Furthermore, cell cycle analysis indicated that CLU knockdown reinforced the efficacy of epirubicin on G0/G1 cell cycle arrest. Taken together, our results suggest that CLU silencing enhances chemosensitivity of EJ bladder cancer cells to epirubicin. Lentivirus-mediated shRNA targeting CLU may be an alternative approach in the treatment of bladder cancer. |
| Databáze: | OpenAIRE |
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