桔梗配伍不同治则中药对乳腺癌肺转移的影响

Effects of platycodon in combination with different active ingredients of Chinese herbs on lung metastasis of breast cancer

目的探讨肺经引经药桔梗配伍不同治则中药对乳腺癌肺转移的影响。方法乳腺癌高转移4T1细胞接种于BALB/c小鼠第二对乳房脂肪垫建立乳腺癌肺转移模型,随机分组,于接种后第5天开始灌胃,给予桔梗及桔梗配伍不同治则中药煎剂28天后,处死小鼠。通过肺转移灶定量分析考察小鼠肺转移情况;通过蛋白质印迹(Western Blot)法检测原位瘤及肺转移灶中转化生长因子β1(transforming growth factorβ1,TGFβ1)及相关蛋白Smad4、Smad7的表达。结果与模型组比较,桔梗及其配伍组显著抑制乳腺癌肺转移动物的瘤重(P<0.01),桔梗配伍莪术组效果显著(63.59%),桔梗配伍麦冬组次之(53.25%),桔梗组、桔梗配伍蛇床子组瘤重抑制率分别为42.69%、38.38%。与模型组比较,桔梗及其配伍组动物肺转移灶面积明显减小(P<0.01),但各用药组之间无统计学差异(P>0.05)。与模型组比较,桔梗组原位瘤中TGFβ1、Smad7蛋白表达降低,但无统计学差异;桔梗配伍不同治则中药组TGFβ1、Smad7蛋白表达显著降低(P<0.05);同模型组比较,桔梗及桔梗配伍不同治则中药组动物原位瘤中Smad4蛋白表达显著升高(P<0.01)。与模型组比较,桔梗及桔梗配伍不同治则中药组动物肺转移灶中Smad7蛋白表达降低(P<0.05);桔梗配伍不同治则中药组动物肺转移灶中TGFβ1蛋白表达降低(P<0.05);桔梗配伍不同治则中药组动物肺转移灶中Smad4蛋白表达升高(P<0.01)。结论桔梗及桔梗配伍不同治则中药对乳腺癌肺转移动物有明显的治疗作用,其机制可能与下调TGFβ1、Smad7蛋白的表达有关。

Objective To investigate the effects of platycodon in combination with different active ingredients of Chinese herbs on lung metastasis of breast cancer. Method We inoculated 4T1 cell on the second mammary fat pad of mice to establish the model of lung metastasis. We have garaged the mice with Chinese medicine decoction for 28 days after 5 days of model development. The expression of lung metastasis was quantitatively analyzed. The expression of TGFβ1, Smad4, Smad7 on lung metastasis and tumor in different groups was detected through Western Blot. Result Platycodon and platycodon in combination with different active ingredients of Chinese herbs could inhibit the tumor weight significantly in contrast with the control group （P 〈 0. 01 ） , the first combination is with rhizoma curcumae （63.59%） , the second one is with ophiopogon japonicus （53.25%）, and the inhibition rate of platycodon group as well as platycodon plus cnidium monnieri group is 42. 69% and 38.38% , respectively. Comparing with control group, the areas of lung metastasis in platycodon group and platycodon in combination with different active ingredients of Chinese herbs are smaller （P 〈0. 01 ） , but the differences in the group of platycodon and platycodon in combination with different active ingredients of Chinese herbs are not significant （ P 〉 0. 05 ）. Comparing with control group, the expressions of TGF[31 and Smad7 on tumor in the platycodon group were lower, but the differences were not statistically significant; and the expressions of TGFβ1 and Smad7 on tumor in the group of platycodon in combination with different active ingredients of Chinese herbs are not significant （ P 〈0. 05 ）. In addition, the expressions of Smad4 on tumor in the group of platycodon in combination with different active ingredients of Chinese herbs were higher than that in control group （ P 〈 0. 01 ）. However, the expressions of TGFβ1 and Smad7 on lung metastasis in the group of platycodon in combination with different active ingredients of Chinese herbs were lower （ P 〈0. 05 ）, and the expressions of Smad4 were higher （ P 〈 0. 01 ）. Conclusion The optimized combinations of platycodon with three different active ingredients of Chinese herbs under different therapeutic principles can significantly inhibit lung metastasis of breast cancer, which might be associated with the down-regulation of expressions of TGFβ1 and Smad7.