桂芍茶提取物抑制裸鼠胃癌生长并延长其生存时间。
Gui Shao Tea Extracts Inhibit Gastric Cancer Growth and and Prolong Survival in Nude Mice.
机构信息
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, 510515 Guangzhou, Guangdong, China.
The 2016 Class, 8-Year Program, The First Clinical Medical School, Southern Medical University, 510515 Guangzhou, Guangdong, China.
出版信息
Front Biosci (Landmark Ed). 2022 Aug 18;27(8):250. doi: 10.31083/j.fbl2708250.
BACKGROUND
Gui Shao Tea (GST), a long-aged tea with a Chinese herbal aroma, can treat many stubborn and malignant diseases, according to traditional Chinese medicine. This research aimed to discover and define GST, study the anti-gastric cancer effects of GST extracts and preliminarily elucidate the mechanism of action in the PI3K/Akt signaling pathway and the gut microbiota.
METHODS
GST was analyzed by GC/MS and HPLC. Cell proliferation, the cell cycle and apoptosis were evaluated by a CCK8 assay and flow cytometry. The effects of GST extracts on tumor inhibition and survival time were explored by a gastric cancer xenograft model in nude mice. The PI3K/Akt signaling pathway was assessed by western blotting and immunohistochemistry. Gut microbiota detection and fecal microbiota transplantation were performed to examine whether the tumor inhibition observed in mice was related to gut microbiota changes.
RESULTS
The ingredients in GST, mostly terpenes and their derivatives, were novel and more concentrated than those in tea made from the branches and leaves of the same plant species, , picked and produced the same year, while the levels of polyphenols and alkaloids were significantly reduced. In BGC-823, MGC-803, and SGC-7901 gastric cancer cells, GST extracts significantly inhibited proliferation ( = 0.037), induced G0/G1 arrest ( < 0.001) and promoted early apoptosis ( = 0.041). In mice, gastric tumor growth was significantly inhibited in both the high-dose (HTF) and middle-dose (MTF) GST-fed groups. The inhibition rate in the HTF group was 33.77% on Day 14 ( = 0.042), and that in the MTF group was 55.21% on Day 14 ( = 0.002) and 61.6% on Day 28 ( = 0.008). The survival time of MTF group mice was significantly prolonged by 22.2% ( = 0.013). GST extracts inhibited the PI3K/AKT signaling pathway in gastric cancer cells ( = 0.016) and tissues ( = 0.029), downregulated the protein p-Rb and further downregulated E2F1, thereby affecting the cell cycle and proliferation. GST extracts altered the gut microbiota in mice, but these alterations alone were insufficient to inhibit gastric cancer growth.
CONCLUSIONS
We confirmed the anti-gastric cancer effects of GST extracts, which might provide new approaches and methods for research and development of gastric cancer drugs.
背景
桂梢茶（GST）是一种具有中药香气的陈年老茶，据中医记载，它可以治疗许多顽固性和恶性疾病。本研究旨在发现和定义 GST，研究 GST 提取物的抗胃癌作用，并初步阐明其在 PI3K/Akt 信号通路和肠道微生物群中的作用机制。
方法
采用 GC/MS 和 HPLC 对 GST 进行分析。通过 CCK8 检测和流式细胞术评估细胞增殖、细胞周期和细胞凋亡。通过裸鼠胃癌移植瘤模型研究 GST 提取物对肿瘤抑制和生存时间的影响。通过 Western blot 和免疫组化评估 PI3K/Akt 信号通路。进行肠道微生物检测和粪便微生物移植，以检查在小鼠中观察到的肿瘤抑制是否与肠道微生物群变化有关。
结果
GST 中的成分主要是萜类及其衍生物，比同年采摘和生产的同一种植物的枝叶制成的茶中的成分更新颖、更集中，而多酚和生物碱的水平则明显降低。在 BGC-823、MGC-803 和 SGC-7901 胃癌细胞中，GST 提取物显著抑制增殖（ = 0.037），诱导 G0/G1 期阻滞（ < 0.001）并促进早期凋亡（ = 0.041）。在小鼠中，高剂量（HTF）和中剂量（MTF）GST 喂养组均显著抑制胃肿瘤生长。HTF 组在第 14 天的抑制率为 33.77%（ = 0.042），MTF 组在第 14 天和第 28 天的抑制率分别为 55.21%（ = 0.002）和 61.6%（ = 0.008）。MTF 组小鼠的生存时间延长了 22.2%（ = 0.013）。GST 提取物抑制胃癌细胞（ = 0.016）和组织（ = 0.029）中的 PI3K/AKT 信号通路，下调蛋白 p-Rb，并进一步下调 E2F1，从而影响细胞周期和增殖。GST 提取物改变了小鼠的肠道微生物群，但这些改变本身不足以抑制胃癌的生长。
结论
我们证实了 GST 提取物的抗胃癌作用，这可能为胃癌药物的研究和开发提供新的方法和途径。
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