胃復方對人胃癌BGC-823細胞移植瘤裸鼠作用及其對c-Myc、人端粒酶逆轉錄酶基因表達的影響

張順榮 李東芳 何寄琴

摘要 目的：觀察胃復方對人胃癌BGC-823裸鼠的抑瘤作用及c-Myc、人端粒酶逆轉錄酶（hTERT）基因表達的影響，評估胃復方作用及其可能的作用機制。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只荷瘤鼠隨機分為5組（n=8）：模型對照組、胃復方低劑量組、胃復方高劑量組、氟尿嘧啶組、氟尿嘧啶聯合中藥組，連續給藥4周。每7天記錄腫瘤長徑、短徑，計算瘤體體積并繪制腫瘤生長曲線圖;給藥4周后處死所有荷瘤鼠，剝離皮下移植瘤，稱瘤重、計算抑瘤率;免疫組織化學法檢測瘤體組織c-Myc、hTERT蛋白表達。結果：1）胃復方對人胃癌BGC-823裸鼠移植瘤具有明顯抑制作用，各劑量間有量效關系。其中胃復方低劑量組、胃復方高劑量組、氟尿嘧啶組、氟尿嘧啶聯合中藥組的抑瘤率分別為21.06%、45.89%、30.65%、59.42%。氟尿嘧啶聯合中藥組效果最好。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，差異有統計學意義（P<0.05）;其中氟尿嘧啶聯合中藥組降低明顯。3）腫瘤生長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，差異有統計學意義（P<0.05）。4）與模型組比較，藥物組均能下調c-Myc、hTERT蛋白表達量，差異有統計學意義（P<0.05），其中氟尿嘧啶聯合中藥組下降最明顯。結論：胃復方能夠抑制人胃癌BGC-823細胞BALB/c-nu裸鼠皮下移植瘤生長，可能與下調c-Myc、hTERT蛋白表達有關，并且與氟尿嘧啶聯合用藥有增效作用。

關鍵詞 胃復方;胃癌BGC-823細胞;移植瘤;c-Myc基因;人端粒酶逆轉錄酶基因

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：R242;R735.2 文獻標識碼：A doi：10.3969/j.issn.1673-7202.2019.10.016

據最新流行病學統計顯示，2015年我國胃癌估計發病率為679.1/10萬，估計死亡率為498.0/10萬，高居惡性腫瘤發病率和死亡率的第2位[1]。鑒于胃癌早期癥狀隱匿，診斷較困難，導致國內胃癌的早期確診率低于10%[2]，就診時超過8O%的胃癌患者為進展期胃癌[3]。常規化療不良反應大，長期治療會導致患者耐受性下降，影響臨床療效[4]。近年來國內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。……