Involvement of apoptosis and autophagy in reducing mouse hepatoma ML-1 cell growth in inbred BALB/c mice by bacterial fermented soybean products.
Involvement of apoptosis and autophagy in reducing mouse hepatoma ML-1 cell growth in inbred BALB/c mice by bacterial fermented soybean products.
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DOI：
10.1016/j.fct.2010.08.017
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
C. Su;Fang-Nan Chen;S. Won
中科院分区：
文献类型：
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作者：
C. Su;Fang-Nan Chen;S. Won
根据我们之前的体外报告（Food Chem. Toxicol., 2007）的结果，使用同系动物模型证明了含有活细菌（SCB）的大豆发酵产品的功效。将源自近交系动物且在 BALB/c 小鼠中致瘤的小鼠 HBV 相关肝癌 ML-1 细胞在第 0 天皮下植入 BALB/c 小鼠的胁腹。植入三天后，每天口服 SCB（1.0 或 1.3ml/小鼠/天）或媒介物（水）直至第 60 天。结果表明，SCB 显着降低（P<0.05） 实验期间肿瘤的体积和重量。对肿瘤切片进行TUNEL染色检查，发现接受SCB的小鼠中出现核DNA双链断裂的细胞凋亡现象。免疫组织化学进一步揭示了自噬 LC3-II 点状模式。值得注意的是，SCB 在不存在或存在细胞凋亡的情况下诱导自噬，而细胞凋亡仅在与自噬结合的情况下观察到。使用自噬抑制剂的体外研究表明，自噬的诱导促进了细胞凋亡。这些数据表明，口服 SCB 对肿瘤体积和肿瘤重量的抑制是由于诱导细胞凋亡和自噬性细胞死亡，这表明 SCB 对 HBV 相关 HCC 具有治疗潜力。
Followed by the results of our previous in vitro report (Food Chem. Toxicol., 2007), the efficacy of the soybean fermentation products containing live bacteria (SCB) was demonstrated using a syngeneic animal model. Murine HBV-related hepatoma ML-1 cells, derived from inbred animals and tumorigenic in BALB/c mice, were implanted subcutaneously to the flank of BALB/c mice on day 0. Three days after implantation, SCB (1.0 or 1.3ml/mouse/day) or vehicle (water) was orally administrated daily until day 60. The results indicate that SCB significantly reduced (P<0.05) the volumes and weights of tumors during the experimental periods. Examination using TUNEL staining on section of tumors revealed apoptotic phenomenon of nuclear DNA double-strand breaks in the groups of mice received SCB. Immunohistochemistry further revealed an autophagic LC3-II punctate pattern. Of note, SCB induced autophagy in the absence or presence of apoptosis, whereas, apoptosis was observed only in combination with autophagy. In vitro study using autophagy inhibitor indicated that the induction of autophagy promoted apoptosis. These data imply that the suppression in tumor volumes and tumor weights by oral administration of SCB was due to the induction of apoptotic and autophagic cell death, which suggests therapeutic potential of SCB on HBV-related HCC.