West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, China.
Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China.
BMC Complement Med Ther. 2021 May 8;21(1):137. doi: 10.1186/s12906-021-03301-6.
Natural products, especially those with high contents of phytochemicals, are promising alternative medicines owing to their antitumor properties and few side effects. In this study, the effects of a plant-based medicinal food (PBMF) composed of six medicinal and edible plants, namely, Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa, on gastric cancer and the underlying molecular mechanisms were investigated in vivo.
A subcutaneous xenograft model of gastric cancer was successfully established in nude mice inoculated with SGC-7901 cells. The tumor-bearing mice were separately underwent with particular diets supplemented with three doses of PBMF (43.22, 86.44, and 172.88 g/kg diet) for 30 days. Tumor volumes were recorded. Histopathological changes in and apoptosis of the xenografts were evaluated by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, respectively. Serum levels of TNF-α, MMP-2, and MMP-9 were detected by enzyme-linked immunosorbent assay. The mRNA expression levels of β-catenin, GSK-3β, E-cadherin, N-cadherin, MMP-2/9, Snail, Bax, Bcl-2, Caspase-3/9, and Cyclin D1 were evaluated via real-time quantitative polymerase chain reaction. The protein expression levels of GSK-3β, E-cadherin, N-cadherin, and Ki-67 were determined by immunohistochemistry staining.
PBMF treatment efficiently suppressed neoplastic growth, induced apoptosis, and aggravated necrosis in the xenografts of SGC-7901 cells. PBMF treatment significantly decreased the serum levels of MMP-2 and MMP-9 and significantly increased that of TNF-α. Furthermore, PBMF treatment notably upregulated the mRNA expression levels of GSK-3β, E-cadherin, Bax, Caspase-3, and Caspase-9 but substantially downregulated those of β-catenin, N-cadherin, MMP-2, MMP-9, Snail, and Cyclin D1 in tumor tissues. The Bax/Bcl-2 ratio was upregulated at the mRNA level. Moreover, PBMF treatment remarkably increased the protein expression levels of GSK-3β and E-cadherin but notably reduced those of Ki-67 and N-cadherin in tumor tissues.
The PBMF concocted herein exerts anti-gastric cancer activities via epithelial-mesenchymal transition reversal, apoptosis induction, and proliferation inhibition. The underlying molecular mechanisms likely rely on suppressing the Wnt/β-catenin signaling pathway.
天然产物，尤其是那些具有高含量植物化学物质的天然产物，由于其抗肿瘤特性和很少的副作用，是很有前途的替代药物。本研究以 Coix 种子、香菇、芦笋、鱼腥草、蒲公英和灰树花等 6 种药用和食用植物组成的植物药食同源食品（PBMF）为研究对象，探讨其对胃癌的体内作用及其潜在的分子机制。
通过接种 SGC-7901 细胞成功建立了裸鼠皮下胃癌移植瘤模型。将荷瘤小鼠分别用三种剂量的 PBMF（43.22、86.44 和 172.88g/kg 饮食）补充的特殊饮食处理 30 天。记录肿瘤体积。通过苏木精和伊红染色评估异种移植物的组织学变化和细胞凋亡，通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记染色（TUNEL）检测细胞凋亡。通过酶联免疫吸附试验（ELISA）检测血清中 TNF-α、MMP-2 和 MMP-9 的水平。通过实时定量聚合酶链反应（qPCR）评估β-catenin、GSK-3β、E-cadherin、N-cadherin、MMP-2/9、Snail、Bax、Bcl-2、Caspase-3/9 和 Cyclin D1 的 mRNA 表达水平。通过免疫组织化学染色检测 GSK-3β、E-cadherin、N-cadherin 和 Ki-67 的蛋白表达水平。
PBMF 治疗能有效抑制 SGC-7901 细胞异种移植瘤的肿瘤生长，诱导细胞凋亡，加重细胞坏死。PBMF 治疗显著降低了 MMP-2 和 MMP-9 的血清水平，显著增加了 TNF-α 的水平。此外，PBMF 治疗显著上调了肿瘤组织中 GSK-3β、E-cadherin、Bax、Caspase-3 和 Caspase-9 的 mRNA 表达水平，而下调了β-catenin、N-cadherin、MMP-2、MMP-9、Snail 和 Cyclin D1 的表达水平。Bax/Bcl-2 比值在 mRNA 水平上也上调了。此外，PBMF 治疗显著增加了肿瘤组织中 GSK-3β和 E-cadherin 的蛋白表达水平，显著降低了 Ki-67 和 N-cadherin 的蛋白表达水平。
本文所制备的 PBMF 通过上皮间质转化逆转、诱导细胞凋亡和抑制细胞增殖发挥抗胃癌作用。其潜在的分子机制可能依赖于抑制 Wnt/β-catenin 信号通路。
