PEREIRA, JULIANALEVY, DEBORARUIZ, JORGE L.M.BROCARDO, GRACIELA A.FERREIRA, KLEBER A.COSTA, RENATA O.QUEIROZ, RODRIGO G.MARIA, DURVANEI A.HALLACK NETO, ABRAHÃO E.CHAMONE, DALTON A.F.BYDLOWSKI, SÉRGIO P.2014-07-312014-07-312014-07-312014-07-312013PEREIRA, JULIANA; LEVY, DEBORA; RUIZ, JORGE L.M.; BROCARDO, GRACIELA A.; FERREIRA, KLEBER A.; COSTA, RENATA O.; QUEIROZ, RODRIGO G.; MARIA, DURVANEI A.; HALLACK NETO, ABRAHÃO E.; CHAMONE, DALTON A.F.; BYDLOWSKI, SÉRGIO P. Azidothymidine is effective against human multiple myeloma: a new use for an old drug?. <b>Anti-Cancer Agents in Medicinal Chemistry</b>, v. 13, n. 1, p. 186-192, 2013. DOI: <a href="https://dx.doi.org/10.2174/187152013804487416">10.2174/187152013804487416</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/8476.1871-5206http://repositorio.ipen.br/handle/123456789/8476Azidothymidine (AZT) is an antiretroviral drug that affects cell proliferation, apoptosis, and the NF-κB pathway. As multiple myeloma (MM) presents with constitutive activation of NF-κB, we analyzed the effect of AZT on human MM cell lines. We evaluated the cytotoxic effect of AZT in human MM cell lines sensitive (8226/S) or resistant to doxorubicin (8226/DX5) and human T cell lymphoblast-like cells, uterine sarcoma cells, and HUVEC using MTT assay. Cytotoxicity was also evaluated in vivo in nude mice xenografted with 8226/S tumor. The effect of AZT on the expression of genes involved in cell proliferation, apoptosis, angiogenesis, and the NF-κB pathway was analyzed in the xenografts using real-time polymerase chain reaction. AZT was effective against both 8226/S and 8226/DX5 cells in a dose and time-dependent manner (p = 0.02) in vitro and promoted cell cycle arrest in S phase in these cells. The tumor volume was lower in mice treated with AZT compared to untreated mice (p = 0.0003). AZT down-regulated the pro-proliferative genes encoding AKT1, MYC, STAT1, MAPK8, MAPK9, CCL-3, Bcl-3, and cyclin D2; pro-angiogenenic genes encoding VEGF and IL8; and genes involved in cell adhesion (ICAM1 and FN1) and the NF-κB pathway. AZT up-regulated the expression of tumor suppressor gene FOXP1 and the pro-apoptotic genes encoding BID, Bcl-10, and caspase-8. Thus, we demonstrated the cytotoxic effect of AZT in human MM cell lines for the first time. Our data may provide the rationale for future clinical trials of AZT for treating MM.186-192closedAccessneoplasmsplasma cellshemic diseasesmortalityanti-infective agentsviral diseasescell proliferationapoptosisangiogenesistoxicityArtigo de periódico11310.2174/187152013804487416