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    已发表论文

    多西他赛固体脂质纳米颗粒抑制乳腺癌细胞增长，伴减少骨髓抑制毒性

     

    Authors Yuan Q, Han J, Cong WS, Ge Y, Ma DD, Dai ZX, Li YP, Bi XL

    Published Date October 2014 Volume 2014:9(1) Pages 4829—4846

    DOI http://dx.doi.org/10.2147/IJN.S70919

    Received 10 July 2014, Accepted 8 August 2014, Published 17 October 2014

    Approved for publication by Professor Thomas J. Webster

    Abstract: Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs) were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere®) and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly lowering myelosuppression toxicity to bone marrow cells from mice. Taken together, these results expound the antitumor efficacy and the potential working mechanisms of DSNs in its anticancer activity and toxicity, which provide a theoretical foundation to develop and apply a more efficient docetaxel formulation to treat cancer patients.
    Keywords: docetaxel, docetaxel-loaded solid lipid nanoparticles, breast cancer, toxicity





     

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