桦褐孔菌醇提物对胃癌模型裸鼠和BGC－823胃癌细胞Ras/MAPK信号通路的影响

乔羽；项楠；周忠光；刘旭

文章摘要

乔羽；项楠；周忠光；刘旭.桦褐孔菌醇提物对胃癌模型裸鼠和BGC－823胃癌细胞Ras/MAPK信号通路的影响[J].中医药信息,2023,40(11):7-12

桦褐孔菌醇提物对胃癌模型裸鼠和BGC－823胃癌细胞Ras/MAPK信号通路的影响

Effects of Ethanol Extract from Inonotus Obliquus on Ras/MAPK Signaling Pathway of Gastric Cancer Model Nude Mice and BGC－823 Gastric Cancer Cells

投稿时间：2023-09-15 录用日期：2023-10-26

DOI：10.19656/j.cnki.1002-2406.20231102

中文关键词: 桦褐孔菌胃癌 Ras p38MAPK

英文关键词: Inonotus obliquus Gastric cancer Ras p38MAPK

基金项目:黑龙江省教育厅普通本科高等学校青年创新人才支持计划

作者	单位
乔羽；项楠；周忠光；刘旭

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中文摘要:

目的：观察桦褐孔菌醇提物对胃癌模型裸鼠和人系胃癌细胞株BGC-823 Ras/MAPK信号通路相关蛋白表达的干预作用。方法：采用体内与体外实验相结合的方式。体内实验中将49只裸鼠随机分为空白组、模型组、阴性对照组、西药组和桦褐孔菌醇提物高、中、低剂量组。除空白组外，其余6组裸鼠腋下皮肤接种0.2 mL BGC-823细胞（2×107个/mL），建立荷瘤小鼠模型，桦褐孔菌醇提物高、中、低剂量组分别灌胃给予桦褐孔菌醇提物1.56、0.78、0.39 mg/g，西药组灌胃给予卡培他滨0.5 mg/g，阴性对照组灌胃给予CMC溶剂，空白组和模型组不给药，每日1次，连续21 d，免疫组织化学法检测荷瘤裸鼠肿瘤中Ras、JNKS、p38MAPK蛋白表达。体外实验中将对数生长期的BGC-823细胞随机分为模型组、阴性对照组、西药组、高剂量组、中剂量组和低剂量组。模型组给予同体积培养液，阴性对照组给予同体积二甲基亚砜，西药组给予5-氟尿嘧啶120 mg/mL，高、中、低剂量组分别给予桦褐孔菌醇提物0.4、0.2、0.1 mg/mL。RT-PCR和Western blot检测信号通路中的关键因子Raf-1、MEK、ERKs、p38MAPK的表达水平。结果：体内实验中，与模型组比较，各给药组Ras、JNKS、p38MAPK蛋白的阳性表达降低（P <0.01）。体外实验中，与模型组比较，各给药组Raf-1、MEK、p38MAPK基因相对表达量降低（P <0.01）；与模型组比较，西药组与桦褐孔菌醇提物处理后的高、中剂量组ERKs基因相对表达量降低（P <0.01）；与模型组比较，各给药组p-Raf-1、p-MEK、p-ERKs和p-p38MAPK表达水平降低（P <0.01）。结论：桦褐孔菌醇提物可能通过下调Ras、JNKS和p38MAPK表达，抑制Ras/MAPK信号通路的活化，从而延缓胃癌病情发展。

英文摘要:

Objective: To observe the intervention effect of ethanol extract of inonotus obliquus on the expression of Ras/MAPK signaling pathway related proteins in gastric cancer model nude mice and human gastric cancer cell line BGC-823. Methods: This study was conducted through combining in vivo and in vitro experiments. For in vivo experiments, 49 nude mice were randomly divided into blank group, model group, negative control group, Western medicine group, and inonotus obliquus alcohol extract low, medium and high dose groups. Except for the blank group, the remaining 6 groups of nude mice were inoculated with 0. 2 mL of BGC-823 cells on their axillary skin(2 × 107/mL) to establish tumor bearing mouse model. The high, medium, and low dose groups of inonotus obliquus alcohol extract were gavaged with 1. 56, 0. 78, and 0. 39 mg/g of inonotus obliquus alcohol extract respectively, the Western medicine group was given 0. 5 mg/g of capecitabine by gavage, and the negative control group was given CMC solvent by gavage, once a day for 21 consecutive days, and the blank group and model group were not given medication. Immunohistochemistry was used to detect the expressions of Ras, JNKS, and p38MAPK proteins in tumor bearing nude mice. In vitro experiments, BGC-823 cells with logarithmic growth phase were randomly divided into model group, negative control group, Western medicine group, and high-dose, medium dose, and low-dose groups. The model group was given the same volume of culture medium, the negative control group was given the same volume of dimethyl sulfoxide, the Western medicine group was given 120 mg/mL of 5-fluorouracil, and the high, medium, and low dose groups were given 0. 4, 0. 2, and 0. 1 mg/mL of ethanol extract of inonotus obliquus respectively. RT PCR and Western blot were used to detect the expression levels of key factors Raf-1, MEK, ERKs, and p38MAPK in the signaling pathway. Results: In vivo experiments, compared with the model group, the positive expression of Ras, JNKS, and p38MAPK proteins in each treatment group decreased(P <0. 01). In vitro experiments, compared with the model group, the relative expression levels of Raf-1, MEK, and p38MAPK genes in each treatment group decreased(P < 0. 01). Compared with the model group, the relative expression of ERKs gene in Western medicine group and the high and medium dose groups of inonotus obliquus alcohol extract decreased(P < 0. 01). Compared with the model group, the expression levels of p-Raf-1, pMEK, p-ERKs and p-p38MAPK in each treatment group were decreased(P < 0. 01). Conclusions: The ethanol extract of inonotus obliquus may inhibit the activation of Ras/MAPK signaling pathway by down-regulating the expression of Ras, JNKS and p38MAPK, thus delaying the development of gastric cancer.

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