Shi Fang, Li Jinglei, Ye Ziyang, Yang Liuqing, Chen Tingting, Chen Xue, Ye Ming
School of Food Science and Engineering , Hefei University of Technology , Hefei 230009 , China . Email:
Medchemcomm. 2018 May 16;9(6):1059-1068. doi: 10.1039/c8md00035b. eCollection 2018 Jun 1.
In the present study, we investigated the anti-tumor activities of the intracellular homogeneous melanin (LM) of YM226 and its derivative (ALM) on liver cancer using murine H22 hepatocarcinoma model. The results showed that LM and ALM (50 and 200 mg kg) could effectively inhibit tumor growth of H22 tumour-bearing mice. The body weight, liver, spleen and thymus indices also improved in the LM and ALM treated groups. Moreover, the levels of alanine aminotransferase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), creatinine (CRE), blood urea nitrogen (BUN) and uric acid (UA) were lowered. Serum cytokines of interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were increased on LM and ALM administration, while LM and ALM significantly decreased the vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels. The H&E staining indicated that LM and ALM exhibited antitumor activity by promoting apoptosis and inhibiting angiogenesis. The anti-tumor effect of ALM was more significant than that of LM for the same dose. In summary, the findings demonstrated that LM and ALM might be promising candidates for the prevention and treatment of HCC.
在本研究中，我们使用小鼠H22肝癌模型研究了YM226的细胞内均质黑色素（LM）及其衍生物（ALM）对肝癌的抗肿瘤活性。结果表明，LM和ALM（50和200 mg/kg）可有效抑制H22荷瘤小鼠的肿瘤生长。LM和ALM治疗组的体重、肝脏、脾脏和胸腺指数也有所改善。此外，丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）、肌酐（CRE）、血尿素氮（BUN）和尿酸（UA）水平降低。给予LM和ALM后，血清白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）细胞因子增加，而LM和ALM显著降低血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）水平。苏木精-伊红染色表明，LM和ALM通过促进凋亡和抑制血管生成表现出抗肿瘤活性。相同剂量下，ALM的抗肿瘤作用比LM更显著。总之，研究结果表明，LM和ALM可能是预防和治疗肝癌的有前景的候选药物。
