复方开口箭合剂对乳腺癌生长转移的影响

Effects of Compound Kaikoujian Mixture on Growth,Metastasis and mTOR Expression of Breast Cancer

目的:研究复方开口箭合剂对乳腺癌生长转移的作用及其机制。方法:60只BALB/C小鼠随机分为空白对照组、模型组、依维莫司组(2 mg·kg^(-1))及复方开口箭合剂高(60 g·kg^(-1))、中(30 g·kg^(-1))、低(15 g·kg^(-1))剂量组,每组10只。除空白对照组外,其余组小鼠乳垫下接种50μL密度为1×10;mL;的4T1细胞悬液建立乳腺癌模型,空白对照组小鼠乳垫下注射等量生理盐水。造模成功后,复方开口箭合剂各给药组分别以10 mL·kg^(-1)的体积灌胃给予相应药物,空白对照组及模型组灌胃给予等体积生理盐水,每日1次;依维莫司组腹腔注射依维莫司溶液,每周2次,连续给药14 d。分别在给药第7天和第14天时,检测各组小鼠的瘤质量,计算抑瘤率;显微镜下观察肺转移结节情况,计数结节数目,计算肺转移抑制率;采用RT-PCR测定乳腺原位瘤组织mTOR mRNA的表达水平。结果:与给药7 d后比较,给药14 d后,模型组瘤质量、肺组织中转移性结节数显著增加;复方开口箭合剂低剂量组瘤质量及肺组织中转移性结节数显著增加,mTOR mRNA的表达水平显著降低;复方开口箭合剂中剂量组瘤质量显著降低,肺组织中转移性结节数显著增加;复方开口箭合剂高剂量组瘤质量及mTOR mRNA的表达水平显著降低,肺组织中转移性结节数显著减少。与空白对照组比较,模型组mTOR mRNA的表达水平均显著升高。与模型组比较,各给药组小鼠的瘤质量及mTOR mRNA的表达水平均显著降低,肺组织中转移性结节数显著减少,抑瘤率及肺转移抑制率有所提高,差异均具有统计学意义。结论:复方开口箭合剂可有效抑制乳腺癌的生长及肺转移,其作用可能与抑制mTOR表达相关。

Objective:To investigate the effect of Compound Kaikoujian mixture on the growth and metastasis of breast cancer and its mechanism.Methods:60 BALB/C mice were randomly divided into blank control group,model group,everolimus group(2 mg·kg^(-1)) and Compound Kaikoujian mixture high(60 g·kg^(-1)),medium(30 g·kg^(-1)),low(15 g·kg^(-1)) dose group,10 in each group.Except for the blank control group,mice in other groups were inoculated with 50 μL of 4 T1 cell suspension with a density of 1×10~6 mL;under the breast pad to establish a breast cancer model,while the mice in the blank control group were injected with the same volume of normal saline under the breast pad.After successful modeling,each administration group of Compound Kaikoujian mixture was given corresponding drugs by intragastric administration at a volume of 10 mL·kg^(-1),and the blank control group and model group were intragastrically administered with an equal volume of normal saline,once a day.The everolimus group was intraperitoneally injected with everolimus solution twice a week for 14 consecutive days.On the 7 th and 14 th days of the administration,the tumor mass of mice in each group was detected,and the tumor inhibition rate was calculated.The lung metastases were observed,the number of nodules was counted,and the lung metastasis inhibition rate was calculated under a microscope.And RT-PCR was used to determine the expression level of mTOR mRNA in situ tumor tissue of the breast.Results:Compared with 7 days after administration,after 14 days of the administration,the tumor mass and the number of metastatic nodules in the lung tissue in the model group increased significantly.In the low-dose Compound Kaikoujian mixture group,tumor mass and mTOR mRNA expression level were significantly decreased,and the number of metastatic nodules in lung tissue was significantly increased.In the middle-dose Compound Kaikoujian mixture group,the tumor mass was significantly decreased,and the number of metastatic nodules in the lung tissue was significantly increased.In the high-dose Compound Kaikoujian mixture group,tumor mass and mTOR mRNA expression level were significantly reduced,and the number of metastatic nodules in lung tissue was significantly decreased.Compared with the blank control group,the expression level of mTOR mRNA in the model group was significantly increased.Compared with the model group,the tumor mass and mTOR mRNA expression level of the mice in each administration group were significantly reduced,the number of metastatic nodules in the lung tissue was significantly reduced,and the tumor inhibition rate and lung metastasis inhibition rate were improved,and the differences were all statistically significant.Conclusion:Compound Kaikoujian mixture can effectively inhibit the growth and lung metastasis of breast cancer,and its effect may be related to the inhibition of mTOR expression.