Tumor-suppressing potential of stingless bee propolis in in vitro and in vivo models of differentiated-type gastric adenocarcinoma
Tumor-suppressing potential of stingless bee propolis in in vitro and in vivo models of differentiated-type gastric adenocarcinoma
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DOI：
10.1038/s41598-019-55465-4
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发表时间：
2019-12-23
影响因子：
4.6
通讯作者：
Kyuwa, Shigeru
中科院分区：
文献类型：
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作者：
Desamero, Mark Joseph;Kakuta, Shigeru;Kyuwa, Shigeru
蜂胶对多种疾病的保护作用早已被认识到，但这种来自菲律宾无刺蜂的生物活性物质的抗肿瘤功效仍然知之甚少。在这里，我们在体外胃癌模型中展示了菲律宾无刺蜂蜂胶（EEP）粗乙醇提取物的抑瘤潜力，突出了其对分化型人胃癌细胞系的显著亚型特异性，而不是扩散型胃癌细胞系。从机制上讲，这涉及到几个细胞周期相关基因转录物的深刻调节，这与G0/G1期显著的细胞周期阻滞有关。为了加强我们的数据，我们将一种独特的分化型胃癌模型A4gnt KO小鼠与年龄匹配的60周龄C57BL/6 J小鼠随机分为连续30天接受蒸馏水或EEP治疗组。脑电图治疗导致胃幽门肿瘤的大体和组织学病变显著消退，这与细胞周期成分的特异性转录调控一致。此外，p21蛋白的大量表达以及brdu标记的s期细胞快速分裂的显著减少明确地支持了我们的观察结果。总之，这些发现支持菲律宾无刺蜂胶作为分化型胃癌的一种有希望的辅助治疗选择的作用。
The protective property of propolis across a wide spectrum of diseases has long been realized, yet the anti-tumor efficacy of this bioactive substance from Philippine stingless bees has remained poorly understood. Here, we showed the tumor-suppressing potential of crude ethanolic extract of Philippine stingless bee propolis (EEP) in in vitro models of gastric cancer highlighting the first indication of remarkable subtype specificity towards differentiated-type human gastric cancer cell lines but not the diffuse-type. Mechanistically, this involved the profound modulation of several cell cycle related gene transcripts, which correlated with the prominent cell cycle arrest at the G0/G1 phase. To reinforce our data, a unique differentiated-type gastric cancer model, A4gnt KO mice, together with age-matched 60 week-old C57BL/6 J mice were randomly assigned to treatment groups receiving distilled water or EEP for 30 consecutive days. EEP treatment induced significant regression of gross and histological lesions of gastric pyloric tumors that consistently corresponded with specific transcriptional regulation of cell cycle components. Also, the considerable p21 protein expression coupled with a marked reduction in rapidly dividing BrdU-labeled S-phase cells unequivocally supported our observation. Altogether, these findings support the role of Philippine stingless bee propolis as a promising adjunct treatment option in differentiated-type gastric cancer.