二氢杨梅素对乳腺癌模型小鼠的抑瘤作用及其对小鼠肝、肾毒性的影响
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摘要
目的观察二氢杨梅素对MCF-7乳腺癌模型小鼠的抑瘤作用及其对小鼠肝、肾毒性的影响。方法 MCF-7细胞株种植到裸鼠体内,建立MCF-7乳腺癌模型小鼠。将建模成功的12只模型鼠随机编号,分2组,每组6只,分别为常规饲养组(A组)、二氢杨梅素实验组(B组)。A组每日给予足量饵料外同时给予1mL生理盐水(安慰剂)灌胃,B组每日给足量饵料外同时给予含有二氢杨梅素与生理盐水混合的半流质1mL灌胃,二氢杨梅素使用剂量为25mg/g(小鼠体重),每日1次。半自动生化分析仪测定血药浓度和心、肝、肾功能,指标包括乳酸脱氢酶(LDH)、肌酸激酶(CK)、谷丙转氨酶(ALT)、谷草转氨酶(AST)和肌酐(Cr)。喂养2周后处死全部实验小鼠,测量瘤体体积及质量。结果二氢杨梅素25mg/g·d剂量灌胃对模型小鼠无显著毒副作用,且血药浓度可维持在较理想范围。经2周饲养后,实验组较对照组小鼠肿瘤体积明显缩小(953±105)mm~3vs(467±65)mm~3(P<0.05),肿瘤质量显著降低(2.63±0.55)g vs(1.49±0.47)g(P<0.05),抑瘤率达43.35%。两组小鼠血清LDH、CK、ALT、AST、Cr水平无显著差异。结论二氢杨梅素口服给药可以有效抑制乳腺癌荷瘤小鼠的肿瘤生长,对小鼠的心、肝、肾功能均无显著影响。
Objective To observe the antitumor effect of dihydromyricetin on McF-7 breast cancer model mice, and evaluate its hepatic and renal toxicity.Methods MCF-7 cell lines were injected into nude mice to establish MCF-7 breast cancer model. Twelve model mice that were successfully established and randomly divided into two groups, the control group(group A) and the experimental group(group B), 6 mice in each group, respectively. In addition to routine feeding, the experimental group was gradually given dihydromyricetin 5 mg/g(mice weight, the same below), 10 mg/g, 15 mg/g, 20 mg/g, 25 mg/g, 30 mg/g. The drug was given by intra-gastric administration through mouth once a day, and blood drug concentration and heart, liver and kidney function were measured at 6 hours using semi-automatic biochemical analyzer after drug administration. Indicators included lactate dehydrogenase(LDH), creatine kinase(CK), alanine aminotransferase(ALT), aspartate aminotransferase(AST) and creatinine(Cr) were measured. All of the mice were sacrificed 2 weeks later, and the tumor volume and mass were measured.Results Dihydromyricetin at 25 mg/g/d had no significant toxic and side effects on the model mice, and the blood drug concentration could be maintained in an ideal range. 2 weeks later, the tumor volume of the experimental group was significantly reduced(953±105)mm~3 vs(467±65)mm~3(P<0.05), the tumor quality was significantly reduced [(2.63±0.55)g vs(1.49±0.47)g, P<0.05], and the tumor inhibition rate reached 43.35%. There were no significant differences in serum LDH, CK, ALT, AST and Cr levels between the two groups.Conclusion Oral administration of dihydromyricetin can effectively inhibit tumor growth in breast cancer model mice, and has no significant effect on heart, liver and kidney functions.
Objective To observe the antitumor effect of dihydromyricetin on McF-7 breast cancer model mice, and evaluate its hepatic and renal toxicity.Methods MCF-7 cell lines were injected into nude mice to establish MCF-7 breast cancer model. Twelve model mice that were successfully established and randomly divided into two groups, the control group(group A) and the experimental group(group B), 6 mice in each group, respectively. In addition to routine feeding, the experimental group was gradually given dihydromyricetin 5 mg/g(mice weight, the same below), 10 mg/g, 15 mg/g, 20 mg/g, 25 mg/g, 30 mg/g. The drug was given by intra-gastric administration through mouth once a day, and blood drug concentration and heart, liver and kidney function were measured at 6 hours using semi-automatic biochemical analyzer after drug administration. Indicators included lactate dehydrogenase(LDH), creatine kinase(CK), alanine aminotransferase(ALT), aspartate aminotransferase(AST) and creatinine(Cr) were measured. All of the mice were sacrificed 2 weeks later, and the tumor volume and mass were measured.Results Dihydromyricetin at 25 mg/g/d had no significant toxic and side effects on the model mice, and the blood drug concentration could be maintained in an ideal range. 2 weeks later, the tumor volume of the experimental group was significantly reduced(953±105)mm~3 vs(467±65)mm~3(P<0.05), the tumor quality was significantly reduced [(2.63±0.55)g vs(1.49±0.47)g, P<0.05], and the tumor inhibition rate reached 43.35%. There were no significant differences in serum LDH, CK, ALT, AST and Cr levels between the two groups.Conclusion Oral administration of dihydromyricetin can effectively inhibit tumor growth in breast cancer model mice, and has no significant effect on heart, liver and kidney functions.
引文
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[3] 白倩,谢琦,彭晓莉,等.二氢杨梅素通过抑制甲基转移酶诱导人乳腺癌MCF-7细胞PTEN基因去甲基化[J].第三军医大学学报,2014,36(1):20-24.
[4] 张明亮,潘成武,王岗,等.二氢杨梅素通过抑制胰岛素样生长因子1受体下游磷脂酰肌醇3-激酶/蛋白激酶B信号途径增强赫赛汀对乳腺癌细胞的抑制作用[J].转化医学杂志,2017,6(6):340-344,349.
[5] 甄林林,范萍,王萱仪.人乳腺癌裸鼠移植模型的建立[J].南京医科大学学报,2001(6):509-510,568.
[6] 马林伟,戴小丽,吴红雁,等.二氢杨梅素通过调控鸟嘌呤核苷酸解离抑制因子2对结肠癌生长的抑制作用[J].中国临床药理学杂志,2018,34(24):2840-2843.
[7] 常徽,陈军丽,顾业芸,等.二氢杨梅素通过抑制mTOR信号通路抑制乳腺癌细胞迁移和侵袭[J].第三军医大学学报,2018,40(18):1624-1629.
[8] 胡蓉蓉,徐广涛.二氢杨梅素对顺铂体外抗乳腺癌作用的干预及其机制研究[J].浙江中西医结合杂志,2018,28(3):184-187,166.
[9] 王满英,丁小军,孙扬,等.二氢杨梅素通过STAT3/Bcl-2信号通路促进HNSCC细胞自噬和凋亡[J].中国临床医学,2017,24(4):571-576.