a Department of Radiotherapy , The First Affiliated Hospital of Zhejiang Chinese Medical University , Hangzhou , PR China.
b Department of Oncology , The First Affiliated Hospital of Zhejiang Chinese Medical University , Hangzhou , PR China.
J Drug Target. 2018 Mar;26(3):222-230. doi: 10.1080/1061186X.2017.1354003. Epub 2017 Jul 18.
This study was conducted to evaluate the efficacy and possible mechanism of Brucea javanica oil emulsion (BJOE) on cachexia, by observing changes in related indexes in mice with cachexia and identifying the genes responsible based on gene chip analysis. In the BJOE treatment group, body weight loss, tumour growth and metastasis were found obviously inhibited, food and water intake had markedly increased, and survival time was significantly prolonged, as compared to the control group. Moreover, the BJOE witnessed improvement in body weight, prevention of tumour metastasis and overall increase in survival time, as compared to Indometacin (IND, the positive control medicine). It was also found that TNF-α and IL-6 in serum were significantly lower in both groups of BJOE and IND, than in the control group (p < .01). Based on the gene expression data, seven and six hub genes of BJOE and IND groups were found in the potential prognostic impacts networks, and three common genes comprising of Nmd3, Bcl2 and Nhp2l1 were screened. Thus, BJOE could reduce tumour growth and effectively alleviate cancer cachexia, due to inhibition of pro-inflammatory cytokines. Nmd3, Bcl2, Nhp2l1 may be important drug targets, establishing the role of BJOE in the treatment of lung cancer induced cachexia.
本研究通过观察荷瘤小鼠相关指标的变化，基于基因芯片分析鉴定其相关基因，评价鸦胆子油乳剂（BJOE）对恶病质的疗效及可能机制。BJOE 治疗组小鼠体重减轻、肿瘤生长和转移明显受到抑制，摄食量和饮水量明显增加，生存时间明显延长，与对照组相比。与吲哚美辛（IND，阳性对照药物）相比，BJOE 还能改善体重、预防肿瘤转移和整体提高生存时间。BJOE 和 IND 两组血清 TNF-α和 IL-6 也明显低于对照组（p<.01）。基于基因表达数据，发现 BJOE 和 IND 组的潜在预后影响网络中有 7 个和 6 个枢纽基因，筛选出 3 个共同基因，包括 Nmd3、Bcl2 和 Nhp2l1。因此，BJOE 可通过抑制促炎细胞因子减少肿瘤生长，有效缓解癌症恶病质。Nmd3、Bcl2、Nhp2l1 可能是重要的药物靶点，为 BJOE 治疗肺癌诱导的恶病质奠定了作用。
