益气除痰方对Lewis肺癌小鼠种植瘤细胞周期调控相关因子的影响

Effects of Yiqi Chutan Formula on cycle regulation related factors in mice with Lewis lung cancer cell-bearing

目的:观察益气除痰方对Lewis肺癌小鼠肿瘤生长及细胞周期调控相关因子P16、p21/WIF1/CIP1、蛋白激酶C(PKC)、c-myc的影响。方法:建立C57BL/6小鼠Lewis肺癌种植瘤模型30只,随机分为Lewis肺癌模型组、益气除痰方低剂量组、高剂量组3组,每组10只。灌胃21d后,处死小鼠,检测肿瘤体积、重量,并用免疫组化法观察各组肿瘤组织P16、p21/WIF1/CIP1、PKC、c-myc的表达。结果:各组Lewis肺癌小鼠肿瘤体积、瘤重两两比较差异有统计学意义。其中高剂量组、低剂量组瘤体组织P16相对含量与模型组对比均显著增高(P<0.05,P<0.01);高剂量组与模型组、低剂量组对比p21/WIF1/CIP1含量显著增高(P<0.05,P<0.01)。三组PKC含量两两比较差异均有统计学意义。结论:益气除痰方能抑制小鼠Lewis肺癌的生长,其机制可能与其能通过上调P16、p21/WIF1/CIP1、下调PKC表达引起细胞周期阻滞,延长肿瘤细胞倍增时间相关。

Objective： To investigate the effects of Yiqi Chutan Formula on tumor growth and the cell cycle regulation related factors （P16, p21/WIFI/CIP1, PKC, c-myc） in mice with Lewis lung cancer cell implanted. Methods： 30 C57BL/6 mice were implanted Lewis lung cancer cell and randomly divided into Lewis lung cancer model group, low-dose Yiqi Chutan Formula group （1.0g/kg/d） and high-dose Yiqi Chutan Formula group （3.0g/kg/d）, 10 mice in each group. After accepted intragastric administration for 21 days, mice in the 3 groups were sacrificed for detecting gross tumor volume and weight of the tumor. The expression of P16, p21/WIFI/CIP1, PKC and c-myc in the tumor tissue were evaluated by immunohistochemistry. Results： The tumor volume and weight of the tumor in high-dose Yiqi Chutan Formula group were lower than those in low-dose group, as well dramatic lower than Lewis lung cancer model group. There were statistical significances in comparison between any two groups. The expression of P16 in high-dose Yiqi Cbutan Formula group was higher than in low-dose Yiqi Chutan Formula group, as well dramatic higher than Lewis lung cancer model group. The expression of p21/WlFI/CIPlwas in high-dose Yiqi Chutan Formula group, which was higher than in low-dose Yiqi Chutan Formula group, as well dramatic higher than Lewis lung cancer model group. The expression of PKC in high-dose Yiqi Chutan Recipe group was lower than in low-dose Yiqi Chutan Formula group, as well dramatic higher than Lewis lung cancer model group. There were statistical significances in comparison between any two groups. The expression of C-myc in low-dose Yiqi Chutan Formula group was higher than in high-dose Yiqi Chutan Formula group, as well than Lewis lung cancer model group. Conclusion： The growth of the Lewis lung cancer tissue could be inhibited by Yiqi Chutan Formula. The mechanism might be related to the up-regulation of P16 and p21/WIFI/CIP1 and the down-regulation of PKC, which could inhibit cancer cell growth cycles and extend the multiplication time of tumor tissue.