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  • Enhanced chemosensitivity of drug-resistant osteosarcoma cells by lentivirus-mediated Bcl-2 silencing.

Enhanced chemosensitivity of drug-resistant osteosarcoma cells by lentivirus-mediated Bcl-2 silencing.

Biochemical and biophysical research communications (2009-10-13)
Yao Zhao, Chun-lin Zhang, Bing-fang Zeng, Xiao-san Wu, Tian-tian Gao, Yoshino Oda
要旨

The Bcl-2 gene is frequently overexpressed in malignancy and is responsible for the resistance induced by chemotherapeutic drugs. The aim of this study was to investigate whether the inhibition of Bcl-2 by lentivirus-mediated RNA interference would enhance doxorubicin cytotoxicity in the drug-resistant human osteosarcoma MG63 cells. Downregulation of Bcl-2 was confirmed by quantitative reverse transcription PCR and Western blotting. Moreover, the ratio of Bcl-2/Bax decreased due to the downregulation of Bcl-2 expression and the upregulation of Bax expression. Decreased cyclin D1 expression was also detected. Flow cytometry and MTT assays revealed that Bcl-2 knock-down increased cellular apoptosis and the MG63 cells became sensitive to doxorubicin. However, no detectable alterations in MDR1 or Bcl-xl expression were observed. Therefore, lentivirus-mediated Bcl-2 knock-down may sensitize these human osteosarcoma cells to doxorubicin and provide a potential therapeutic strategy for osteosarcoma.