二氢杨梅素对裸鼠腹腔移植人胃癌细胞中Caveolin-1表达的影响

Effect of Dihydromyricetin on caveolin-1 in nude mouse models of human gastric cancer

摘要:

目的观察二氢杨梅素（DMY）对裸鼠腹腔移植人胃癌细胞生长的抑制作用及对腹腔瘤组织中Caveolin-1表达的影响。方法复制人胃癌腹腔移植的裸鼠模型。将复模成功的24 只裸鼠随机分为4 组，即移植瘤模型组，DMY 低、中及高剂量处理组。分别观察荷瘤裸鼠的腹腔移植瘤的生长和成瘤情况，测量肿瘤的重量、长短径并计算肿瘤的体积。采用免疫组织化学法和Western blot 检测人胃癌腹腔移植瘤腹腔瘤体中Caveolin-1 和Ki67 的表达。结果与移植瘤模型组比较，100 和200 mg/（kg·d）DMY 中、高剂量组腹腔移植瘤成瘤个数，腹腔瘤体的重量及腹腔瘤体的体积均降低，呈现剂量依赖性（P <0.05），裸鼠的食欲、活动情况和精神状态等一般情况改善。与移植瘤模型组比较，100 和200 mg/（kg·d）DMY 中、高剂量组腹腔移植瘤体表达Caveolin-1 的阳性细胞百分率和Caveolin-1 的蛋白表达水平均增加，呈现剂量依赖性（P <0.05）；而Ki67 的阳性细胞百分率和Caveolin-1 的蛋白表达水平均降低，也呈现剂量依赖性（P <0.05）。结论二氢杨梅素以剂量依赖的方式抑制人胃癌腹腔移植瘤的生长，其作用机制可能与上调Caveolin-1 的表达有关。

Abstract:

Objective To investigate inhibitory effect of Dihydromyricetin (DMY) on the growth of gastric cancer and expression of caveolin-1 in nude mouse models of human gastric cancer. Methods Nude mouse models of peritoneal transplanted human gastric cancer was established. Twenty-four successfully transplanted nude mice were randomly divided into 4 groups: tumor group, tumor with low dose group [50 mg/（kg·d）],moderate dose group [100 mg/（kg·d）] and high dose group [200 mg/（kg·d）] of DMY. The growth rate and tumor size were monitored. The expression levels of caveolin -1 and Ki67 in tumors were tested by Immunohistochemistry and Western blot. Results The number, weight, and volume of tumors were significantly decreased in both tumor with moderate and high dose groups dose dependently when compared with the tumor group (P < 0.05). The appetite, activity and mental state of animals in the tumor with moderate and high dose groups were significantly improved in comparison with the tumor group. Immunohistochemistry and Western blot data indicated that the percentage of Caveolin-1 positive cells and expression level of protein Caveolin-1 were significantly increased in the tumor with moderate and high dose groups when compared with the tumor group dose dependently (P < 0.05). Similarly, the percentage of Ki67 positive cells and expression level were significantly increased in the moderate and high dose groups when compared with the tumor group dose dependently (P < 0.05). Conclusions DMY inhibits the growth of peritoneal transplanted human gastric cancer in dose dependent manner and the mechanism may be related to upregulation of Caveolin-1.