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Although molecular targeted therapies have recently been developed and have improved the overall survival, melanoma patients may show no response and acquisition of resistance to these drugs. Thus, other molecular approaches are essential for the treatment of metastatic melanoma. In the present study, we investigated the effect of cotreatment with dacarbazine and statins on tumor growth, metastasis, and survival rate in mice with metastatic melanomas. We found that cotreatment with dacarbazine and statins significantly inhibited tumor growth and metastasis via suppression of the RhoA\/RhoC\/LIM domain kinase\/serum response factor\/c\u2010Fos pathway and enhanced p53, p21, p27, cleaved caspase\u20103, and cleaved poly(ADP\u2010ribose) polymerase 1 expression in vivo. Moreover, the cotreatment significantly improved the survival rate in metastasis\u2010bearing mice. Importantly, treatment with dacarbazine plus 100\u2009mg\/kg simvastatin or fluvastatin prevented metastasis\u2010associated death in 4\/20 mice that received dacarbazine\u2009+\u2009simvastatin and in 8\/20 mice that received dacarbazine\u2009+\u2009fluvastatin (survival rates, 20% and 40%, respectively). These results suggested that cotreatment with dacarbazine and statins may thus serve as a new therapeutic approach to control tumor growth and metastasis in melanoma patients.<\/jats:p>","DOI":"10.1002\/jcp.28430","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:17:34Z","timestamp":1551745054000},"page":"17975-17989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Combination therapy with dacarbazine and statins improved the survival rate in mice with metastatic melanoma"],"prefix":"10.1002","volume":"234","author":[{"given":"Masanobu","family":"Tsubaki","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy Kindai University Faculty of Pharmacy, Kowakae Higoshi\u2010Osaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Takeda","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy Kindai 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