Clarithromycin Synergistically Enhances Thalidomide Cytotoxicity in Myeloma Cells.
Clarithromycin (CAM) is a macrolide antibiotic that is widely used in the treatment of respiratory tract infections, sexually transmitted diseases and infections caused by the Helicobacter pylori and Mycobacterium avium complex. Recent studies showed that CAM was highly effective against multiple myeloma (MM) when used in combination with immunomodulatory drugs and dexamethasone. However, the related mechanism is still unknown. As 3 immunomodulatory agents are all effective in the respective regimen, we postulated that CAM might enhance the effect of immunomodulatory drugs. We evaluated the interaction effects of CAM and thalidomide on myeloma cells. Taking into consideration that thalidomide did not affect the proliferation of myeloma cells in vitro, we cocultured myeloma cells with peripheral blood monocytes and evaluated the effects of CAM and thalidomide on the cocultured cell model. Data showed that thalidomide and CAM synergistically inhibited the proliferation of the cells. On this same model, we also found that thalidomide and CAM synergistically decreased the secretion of tumor necrosis factor-α and interleukin-6. This might be caused by the effect of the 2 drugs on inhibiting the activation of ERK1/2 and AKT. These data suggest that the efficacy of CAM against MM was partly due to its synergistic action with the immunomodulatory agents.
Department of Hematology, Jinling Hospital, Nanjing, China.
Xu-Hua
XH
Qiu
Jing-Jing
JJ
Shao
Jian-Gang
JG
Mei
Han-Qing
HQ
Li
Hong-Qin
HQ
Cao
D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use*; D004357:Drug Synergism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D013792:Thalidomide / Q000627:therapeutic use* / Q000633:toxicity
D007166:Immunosuppressive Agents; D013792:Thalidomide; D017291:Clarithromycin