Synergistic effects of combination treatment with bortezomib and doxorubicin in human neuroblastoma cell lines.
BACKGROUND
Neuroblastoma (NB) is the most common extracranial solid tumor in infants. Currently, the mainstay of NB chemotherapy is combination treatment with some traditional drugs, but these combination regimens are always inefficient.


METHODS
The aim of this study was to evaluate the inhibitory effect of a combination of doxorubicin and bortezomib, a novel anticancer drug and the first prote-asome inhibitor approved for the treatment of human malignant tumors, on the proliferation of two human NB cell lines, SK-N-SH and SH-SY5Y. The general mechanism underlying this combined effect was also investigated. Synergistic inhibitory effects on human NB cell proliferation were evaluated using the median-effect principle. The pro-apoptotic effects of these drugs were evaluated using double staining with annexin-V-FITC and propidium iodide.


RESULTS
Synergistic inhibitory effects on proliferation were observed when a combination of bortezomib and doxorubicin was applied to cultured NB cells. A similar synergistic effect on apoptosis was also observed when the two drugs were used concurrently, which suggested that the possible mechanism underlying the observed synergistic inhibitory effect might be related to apoptosis.


CONCLUSIONS
The combination of bortezomib and doxorubicin appears to be a promising strategy to treat NB.
National Laboratory of Medical Molecular Biology, School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China.
Bo-Yu
BY
Du
Wei
W
Song
Lu
L
Bai
Yan
Y
Shen
Shi-Ying
SY
Miao
Lin-Fang
LF
Wang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D004317:Doxorubicin