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Enhanced chemosensitivity by simultaneously inhibiting cell cycle progression and promoting apoptosis of drug-resistant osteosarcoma MG63/DXR cells by targeting Cyclin D1 and Bcl-2.

AIM
To investigate whether the inhibition of Bcl-2 and Cyclin D1 by lentivirus-mediated RNA interference enhances doxorubicin (DXR) cytotoxicity in the drug-resistant human osteosarcoma MG63 cells.


MATERIALS AND METHODS
Lentivirus-mediated RNAi were used to inhibit the expression of Bcl-2 or Cyclin D1 mRNA and protein; qRT-PCR, Western blotting, Flow cytometry and MTT assays were used to detect the expression of Bcl-2 and Cyclin D1 and the sensitivity to doxorubicin of MG63/DXR.


RESULTS
Chronic exposure to DXR induces upregulation of oncogenic Bcl-2 and CyclinD1 in osteosarcoma MG63/DXR cells. Elevated Bax and decreased cyclin D1 was observed in Bcl-2-silenced MG63/DXR cells and decreased Bcl-2 was detected in Cyclin D1-silenced MG63/DXR cells. Individual or simultaneous silencing of Bcl-2/Cyclin D1 enhanced the cytotoxicity of DXR. Furthermore, we detected a synergistic effect of enhanced chemosensitivity by co- silencing Cyclin D1 and Bcl-2.


CONCLUSION
Lentiviral RNAi targeting of Bcl-2 and Cyclin D1 simultaneously could be a potentially more effective therapeutic strategy for osteosarcomas to overcome chemoresistance.