BMS–202和姜黄素共载脂质体在三阴型乳腺癌中的抗肿瘤作用

    Antitumor mechanism of BMS-202 co-loaded liposomes in triple-negative breast cancer

    • 摘要:
      目的: 将姜黄素(curcumin,CUR)和BMS–202作为纳米结构脂质载体(nanostructured lipid carrier,NLC)配方中的脂质核心相结合,评估其对三阴型乳腺癌细胞的影响。
      方法: 制备脂质体共载CUR/BMS–202(CUR/BMS–202–NLC)。体外将MDA–MB–231细胞分为:对照组、游离CUR/BMS–202组、空白–NLC(Blank–NLC)组和CUR/BMS–202–NLC组。分别通过MTT实验、集落形成试验和Transwell试验考察CUR/BMS–202–NLC对MDA–MB–231细胞活力、集落形成和转移的影响。将MDA–MB–231细胞皮下注射到雌性裸鼠的右背侧构建荷瘤BALB/c小鼠模型,小鼠随机分为4组(n = 8):对照组、CUR–NLC组、BMS–202–NLC组和CUR/BMS–202–NLC组。每两天监测一次肿瘤大小和体质量,持续22d。采用免疫组化染色SP法检测CD8、CD4的表达,应用ELISA测定小鼠血清中TNF–α、INF–γ和IL–1β的水平。
      结果: 与Blank–NLC组相比,CUR/BMS–202–NLC组MDA–MB–231的集落形成和细胞迁移数减少(P < 0.05)。与CUR–NLC组和BMS–202–NLC组相比,CUR/BMS–202–NLC组小鼠表现出较高的肿瘤生长抑制。此外,CUR/BMS–202–NLC处理的小鼠表现出肿瘤浸润性CD4和CD8平均阳性细胞数增加和血清中TNF–α、IFN–γ、IL–1β的水平最高(P < 0.05)。
      结论: CUR/BMS–202–NLC在治疗三阴型乳腺癌有潜在的应用价值。

       

      Abstract:
      Objective To evaluate the effects of curcumin (CUR) combined with BMS-202 as the lipid core in the formulation of nanostructured lipid carrier (NLC) on triple negative breast cancer cells.
      Methods Liposomes co-loaded with CUR/BMS-202 (CUR/BMS-202-NLC) were prepared. In vitro, the MDA-MB-231 cells were divided into the control group, free CUR/BMS-202 group, blank-NLC group and CUR/BMS-202-NLC group. The effects of CUR/BMS-202-NLC on the viability, colony formation and metastasis of MDA-MB-231 cells were investigated by MTT assay, colony formation assay and Transwell assay in vitro. MDA-MB-231 cells were injected subcutaneously into the right dorsal side of female nude mice to construct a tumor-bearing BALB/c mouse model. The mice were randomly divided into the control group, CUR-NLC group, BMS- 202-NLC group and CUR/BMS-202-NLC group (8 rats each group). Tumor size and body weight were monitored every two days for 22 days. Tumors were taken for immunohistochemical analysis of CD8 and CD4 expression. The serum levels of TNF-α, INF-γ and IL-1β in four groups were determined using enzyme-linked immunosorbent assay (ELISA).
      Results Compared with the Blank-NLC, the colony formation and cell migration number of MDA-MB-231 in CUR/BMS-202-NLC significantly reduced (P < 0.05). Compared with the CUR-NLC group and BMS-202-NLC group, the CUR/BMS-202-NLC group showed a higher tumor growth inhibition rate. In addition, the tumor-infiltrating CD4 and CD8 staining areas increased, and the serum levels of TNF-α, IFN-γ and IL-1β were the highest in the CUR/BMS-202-NLC-treated mice.
      Conclusions CUR/BMS-202-NLC has potential application value in the treatment of triple-negative breast cancer.

       

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