胡椒碱增强基于 TRAIL 的疗法对三阴性乳腺癌细胞的疗效。
Piperine enhances the efficacy of TRAIL-based therapy for triple-negative breast cancer cells.
机构信息
Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
出版信息
Anticancer Res. 2014 Apr;34(4):1893-9.
BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is most the aggressive type of breast cancer and is poorly responsive to endocrine therapeutics; however, one of the most attractive treatments is tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based therapies. To identify compounds that enhance the efficacy of TRAIL-based therapies, we screened 55 compounds from natural products in combination with TRAIL in TNBC cells.
MATERIALS AND METHODS
Human TNBC cells, MDA-MB-468 and MDA-MB-231, and murine TNBC cells, 4T1, were used. Cell viability, apoptotic cells, and cell cycle were quantified by the WST-1 assay, annexin-V/7-amino-actinomycinD (7-AAD) staining and Propidium iodide (PI) staining, respectively. In vivo effects of piperine were evaluated in the orthotopic-inoculated 4T1-luc mouse model.
RESULTS
After screening, we identified piperine as the most potent adjuvant at enhancing the efficacy of TRAIL-based therapies in TNBC cells in vitro and in vivo, which might be mediated through inhibition of survivin and p65 phosphorylation.
CONCLUSION
Piperine may enhance TRAIL-based therapeutics for TNBC.
背景/目的：三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌类型，对内分泌治疗反应不佳；然而，最有吸引力的治疗方法之一是肿瘤坏死因子相关凋亡诱导配体（TRAIL）为基础的治疗。为了确定增强 TRAIL 为基础的治疗效果的化合物，我们在 TNBC 细胞中用 TRAIL 联合筛选了 55 种天然产物化合物。
材料和方法
使用人 TNBC 细胞 MDA-MB-468 和 MDA-MB-231 以及鼠 TNBC 细胞 4T1。通过 WST-1 测定、膜联蛋白-V/7-氨基放线菌素 D（7-AAD）染色和碘化丙啶（PI）染色分别定量细胞活力、凋亡细胞和细胞周期。在 4T1-luc 荷瘤原位接种的小鼠模型中评估胡椒碱的体内作用。
结果
筛选后，我们确定胡椒碱是体外和体内增强 TRAIL 为基础的 TNBC 细胞治疗效果最有效的佐剂，其可能通过抑制生存素和 p65 磷酸化来介导。
结论
胡椒碱可能增强 TNBC 的 TRAIL 为基础的治疗。
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