黄芩苷抑制错配修复基因缺失的结直肠癌裸鼠原位移植瘤的实验研究

Effects of Baicalin on an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer

目的研究黄芩苷抑制错配修复基因hMLHI缺失的人结肠癌HCT－116细胞在裸鼠原位移植瘤生长、转移的作用。方法建立人结肠癌HCT-116细胞裸鼠荧光原位移植模型。60只荷瘤裸鼠随机分为阴性对照组（G1），50、100、200mg／kg黄芩苷组（C2～G4），每组15只。治疗组分别给予相应剂量的黄芩苷灌胃，每日2次；阴性对照组采用等容量5％NaHCO，灌胃。荧光影像系统下观察原发肿瘤的体积、血管密度以及肿瘤转移情况，并分析实验动物的体质量、生存状况和死亡率。结果药物干预后的第14、21、28天，G2～G4组肿瘤生长速度低于G1组，荧光测量的肿瘤体积（mm^3）明显小于G1（14d：832±637；21d：2012±1566；28d：2494±1557），差异具有统计学意义（F=4．433，P〈0．05），但治疗组间比较差异无统计学意义。实验终点（第28天）时，G2、G3组实验动物的存活率分别为9／15、13／15，生存状态分析显示G3组明显优于G1组和G4组，差异具有统计学意义（x2=4．665、3．980，P〈0．05）；体内开放观察结果显示各组间原发肿瘤的重量、表面血管密度和肿瘤转移情况差异均无统计学意义。结论黄芩苷对错配修复基因hMLH1缺失的结肠癌HCT-116细胞裸鼠原位移植瘤生长具有明显的抑制作用；100mg／kg可能是一个比较理想的治疗剂量。

Objective To study the anticancer effects of Baicalin on an orthotopic transplantation mouse model of mismatch repair gene deficient eolorectal cancer. Methods Sixty orthotopic transplantation mice model of human colon cancer cell line HCT-116 expressing eGFP were established, which were divided randomly into negative controlled group （5% NaHCO3 ） and 50, 100, 200 mg/kg Baicalin groups. The nude mice were treated with intragastrie infusion twice a day. Nude mice growth state, average weigh, inhibition rate of transplanted tumor, tumor metastasis and survival state were observed. Results At 14, 21 and 28 days after treatment with different dose of Baicalin, tumor growth velocity was significantly slower in the treatment groups, and tumor volume was significantly smaller than the controlled group （ there were （832±637） , （2012 ± 1566） and （2494 ± 1557） mm3 respectively in 14, 21 and 28 days） （F =4. 433, P 〈 0. 05）. At the end point of study, survival state of 100 mg/kg group （ 13/15 ） was superior to controlled group （B/15） and 200 mg/kg group （B/15） （X2 = 4. 665 and 3.980, P 〈 0.05）. However, there were no significant differences in tumor metastasis and tumor surface vessel density. Conclusions Baicalin has statistically significant effects in inhibiting tumor growth in an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer, and 100 mg/kg may be an ideal treatment dose.