胃復(fù)方對(duì)人胃癌BGC-823細(xì)胞移植瘤裸鼠作用及其對(duì)c-Myc、人端粒酶逆轉(zhuǎn)錄酶基因表達(dá)的影響

張順榮 李東芳 何寄琴

摘要 目的：觀察胃復(fù)方對(duì)人胃癌BGC-823裸鼠的抑瘤作用及c-Myc、人端粒酶逆轉(zhuǎn)錄酶（hTERT）基因表達(dá)的影響，評(píng)估胃復(fù)方作用及其可能的作用機(jī)制。方法：建立人胃癌BGC-823裸鼠模型;將成功建立的裸鼠胃癌皮下移植瘤模型的40只荷瘤鼠隨機(jī)分為5組（n=8）：模型對(duì)照組、胃復(fù)方低劑量組、胃復(fù)方高劑量組、氟尿嘧啶組、氟尿嘧啶聯(lián)合中藥組，連續(xù)給藥4周。每7天記錄腫瘤長(zhǎng)徑、短徑，計(jì)算瘤體體積并繪制腫瘤生長(zhǎng)曲線圖;給藥4周后處死所有荷瘤鼠，剝離皮下移植瘤，稱瘤重、計(jì)算抑瘤率;免疫組織化學(xué)法檢測(cè)瘤體組織c-Myc、hTERT蛋白表達(dá)。結(jié)果：1）胃復(fù)方對(duì)人胃癌BGC-823裸鼠移植瘤具有明顯抑制作用，各劑量間有量效關(guān)系。其中胃復(fù)方低劑量組、胃復(fù)方高劑量組、氟尿嘧啶組、氟尿嘧啶聯(lián)合中藥組的抑瘤率分別為21.06%、45.89%、30.65%、59.42%。氟尿嘧啶聯(lián)合中藥組效果最好。2）瘤重顯示與模型組比較，各藥物組瘤重均有不同程度的減輕，差異有統(tǒng)計(jì)學(xué)意義（P<0.05）;其中氟尿嘧啶聯(lián)合中藥組降低明顯。3）腫瘤生長(zhǎng)曲線圖顯示與模型組比較，各藥物組瘤體積均有一定程度縮小，差異有統(tǒng)計(jì)學(xué)意義（P<0.05）。4）與模型組比較，藥物組均能下調(diào)c-Myc、hTERT蛋白表達(dá)量，差異有統(tǒng)計(jì)學(xué)意義（P<0.05），其中氟尿嘧啶聯(lián)合中藥組下降最明顯。結(jié)論：胃復(fù)方能夠抑制人胃癌BGC-823細(xì)胞BALB/c-nu裸鼠皮下移植瘤生長(zhǎng)，可能與下調(diào)c-Myc、hTERT蛋白表達(dá)有關(guān)，并且與氟尿嘧啶聯(lián)合用藥有增效作用。

關(guān)鍵詞 胃復(fù)方;胃癌BGC-823細(xì)胞;移植瘤;c-Myc基因;人端粒酶逆轉(zhuǎn)錄酶基因

Abstract Objective：To observe tumor inhibiting effect of Weifu Formula in nude mice with human gastric cancer BGC-823 and its effects on gene expression of C-Myc and hTERT，and to evaluate the effects of Weifu Formula and its possible mechanism of action.Methods：The nude mouse model with human gastric cancer BGC-823 was established.A total of 40 tumor-bearing mice were performed successful modeling for nude mice with subcutaneous xenograft tumor of gastric cancer.They were randomly divided into 5 groups（n=8）：model group，low dose Weifu Formula group，high dose Weifu Formula group，5-Fu group，and 5-Fu combined with Chinese materia medica group，with continuous administration for 4 weeks.Long diameter and short diameter of tumor were recorded every 7 d，tumor volume was calculated and tumor growth curve chart was drawn.All the tumor-bearing mice were killed after 4 weeks of administration，and the subcutaneous xenograft tumor was resected.The tumor was weighed and tumor inhibition rate was calculated.Protein expression of C-Myc and hTERT in tumor tissue was detected by immunohistochemistry.Results：1）Weifu Formula had obvious inhibiting effect on xenograft tumor in nude mice with human gastric cancer BGC-823 and there was dose-effect relationship between different doses.The tumor inhibition rates in the low dose Weifu Formula group，the high dose Weifu Formula group，the 5-Fu group and the 5-Fu combined with Chinese materia medica group were 21.06%，45.89%，30.65% and 59.42%，respectively.Efficacy in the 5-Fu combined with Chinese materia medica group was the best.2）In terms of tumor weight compared with the model group，the tumor weight in each medicine group showed different degrees of decrease（P<0.05）.Among them，the decrease in the 5-Fu combined with Chinese materia medica group was significant.3）The tumor growth curve chart showed that the tumor volume in each medicine group was decreased to some extent compared with the model group（P<0.05）.4）In comparison with the model group，the immunohistochemical results showed that the expression levels of C-Myc and hTERT proteins were decreased in each medicine group（P<0.05），among which the decrease in the 5-Fu combined with Chinese materia medica group was the most obvious.Conclusion：Weifu Formula can inhibit the growth of subcutaneous xenograft tumor in BALB/c-nu nude mice with human gastric cancer BGC-823 cell，which may be related to the down-regulation of C-Myc and hTERT protein expression.And it has synergistic effect when combining with 5-Fu for medication，indicating that Weifu Formula has certain efficacy in human gastric cancer.

Key Words Weifu Formula; BGC-823 cell of gastric cancer; Xenograft tumor; C-Myc; hTERT

中圖分類號(hào)：R242;R735.2 文獻(xiàn)標(biāo)識(shí)碼：A doi：10.3969/j.issn.1673-7202.2019.10.016

據(jù)最新流行病學(xué)統(tǒng)計(jì)顯示，2015年我國(guó)胃癌估計(jì)發(fā)病率為679.1/10萬，估計(jì)死亡率為498.0/10萬，高居惡性腫瘤發(fā)病率和死亡率的第2位[1]。鑒于胃癌早期癥狀隱匿，診斷較困難，導(dǎo)致國(guó)內(nèi)胃癌的早期確診率低于10%[2]，就診時(shí)超過8O%的胃癌患者為進(jìn)展期胃癌[3]。常規(guī)化療不良反應(yīng)大，長(zhǎng)期治療會(huì)導(dǎo)致患者耐受性下降，影響臨床療效[4]。近年來國(guó)內(nèi)外研究者一直致力于靶向及中草藥治療胃癌途徑的探索，為臨床治療胃癌開辟新的思路。……