Aspirin inhibits proliferation and induces apoptosis of multiple myeloma cells through regulation of Bcl-2 and Bax and suppression of VEGF.
OBJECTIVE
Aspirin (ASA) has been frequently used for thromboprophylaxis in patients with multiple myeloma (MM) when treated with thalidomide or lenalidomide. Despite the well-recognized chemopreventive role of ASA in some solid tumors particularly for colon cancer, whether ASA displays the antimyeloma activity remains unclear.


METHODS
MM1.S and RPMI-8226 cell lines harboring K-Ras and N-Ras mutation, respectively, were treated with various concentrations of ASA for different hours. The cell proliferation and apoptosis were performed to explore the effects of ASA on myeloma. Then, the exact mechanisms governing ASA's antimyeloma were explored by qRT-PCR and Western blot. Also, the effect of ASA on tumor growth was observed in NOD/SCID mice bearing myeloma xenografts.


RESULTS
ASA of 0-10 mm concentration inhibits proliferation MM1.S and RPMI-8226 cells in time- and dose-dependent manner. The myeloma cells exposed to ASA treatment displayed concentration-dependent apoptosis, which was closely associated with activation of caspases, upregulation of Bax, and downregulation of Bcl-2 and VEGF. Study in vivo revealed that ASA administration retarded the tumor growth accompanying the survival time of mice bearing myeloma xenografts.


CONCLUSIONS
ASA exerted antiproliferative and pro-apoptotic action in myeloma cells in vitro and delayed the growth of human myeloma cells in vivo. The underlying mechanisms were ascribed to regulation of Bcl-2 and Bax and suppression of VEGF.
Hematology Department, the 1st Affiliated Hospital of Nanchang University, Nanchang, China.
Jiang-Hua
JH
Ding
Li-Ya
LY
Yuan
Rui-Bin
RB
Huang
Guo-An
GA
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D010975:Platelet Aggregation Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D020169:Caspases; D001241:Aspirin
Bax; Bcl-2; VEGF; apoptosis; aspirin; multiple myeloma; proliferation