Enhanced chemosensitivity of drug-resistant osteosarcoma cells by lentivirus-mediated Bcl-2 silencing.
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.
Zhao
Yao
Y
Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200233, China.
Zhang
Chun-lin
CL
Zeng
Bing-fang
BF
Wu
Xiao-san
XS
Gao
Tian-tian
TT
Oda
Yoshino
Y
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D016086:Lentivirus; D012516:Osteosarcoma / Q000188:drug therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D034622:RNA Interference
D000903:Antibiotics, Antineoplastic; D019253:Proto-Oncogene Proteins c-bcl-2; D004317:Doxorubicin