清燥救肺汤对结肠癌增殖侵袭相关蛋白c-myc、EGF、ICAM-1、MMP2、TGF-α表达的影响

Effect of Dryness-Clearing and Lung-Rescuing Decoction on Proliferation and Invasion Related Proteins of C-myc,Epidermal Growth Factor,Intercellular Adhesion Molecule 1, Matrix Metalloproteinase 2 and Transforming Growth Factor α Expression in Colon Carci

【目的】观察清燥救肺汤对小鼠结肠癌CT26细胞增殖相关蛋白原癌基因c-myc,表皮细胞生长因子(EGF)及侵袭相关蛋白细胞间黏附分子1(ICAM-1)、基质金属蛋白酶2(MMP2),转化生长因子α(TGF-α)表达的影响。【方法】将50只雄性BALB/c小鼠随机分为模型组,化疗组,清燥救肺汤高、中、低剂量组,每组10只。右腋下注射CT26细胞建立结肠癌小鼠模型,清燥救肺汤治疗组以15.2、7.6、3.8 g·kg^(-1)·d^(-1)剂量于造模前两周开始灌胃给药,化疗组给予25 mg·kg^(-1)剂量5-氟尿嘧啶(5-FU)腹腔注射,模型组以等体积生理盐水灌胃给药。2周后处死各组小鼠并取瘤组织,称质量计算抑瘤率,以Western-blot法检测EGF,TGF-α,c-myc,ICAM-1及MMP2蛋白表达。【结果】清燥救肺汤高、中剂量组EGF,ICAM-1,MMP2及TGF-α蛋白表达显著降低,与模型组比较,差异均有统计学意义(P<0.05或P<0.01);清燥救肺汤高、中、低剂量组c-myc蛋白表达显著降低,与模型组比较,差异有统计学意义(P<0.05)。【结论】清燥救肺汤可能通过降低EGF、TGF-α及c-myc、ICAM-1、MMP2蛋白表达,发挥抑制荷CT26小鼠结肠癌细胞增殖侵袭的功效。

Objective To observe the effect of Dryness-Clearing Lung-Rescuing Decoction（DLD）on proliferation and invasion related proteins of proto-oncogene c-myc,epidermal growth factor（EGF）,intercellular adhesion molecule 1（ICAM- 1）, matrix metalloproteinase 2（MMP2）, and transforming growth factor α（TGF-α）expression in CT26 colon cancer cells. Methods Fifty male BALB/c mice were randomly divided into model group, chemotherapy group, and high-, middle- and low-dose DLD groups, 10 mice in each group. The colon cancer model was established by injection of CT26 cells into the right armpit. DLD groups were separately given intragastric administration of 15.2,7.6,3.8 g·kg^（-1）·d^（-1） of DLD two weeks before modeling. Chemotherapy group was given injection of 25 mg·kg^（-1）of 5-fluorouracil（5-FU） every other day after modeling. The model group was given intragastric administration of the same volume of saline. After medication for 2 weeks,the mice were killed to obtain the tumor tissues for weighing tumor mass and calculating the tumor-inhibition rate. We determined the expression of c-myc, EGF, ICAM-1, MMP2, and TGF-α by Western blotting method.Results The expression levels of EGF,ICAM-1,MMP2,and TGF-α proteins in high- and middle-dose DLD groups were significantly reduced,the differences being significant compared with those in the model group（P 0.05 or P 0.01）. The expression level of c-myc protein in high-, middle- and low-dose DLD groups was significantly reduced, the difference being significant compared with that in the model group（P 0.05）.Conclusion DLD can significantly inhibit the proliferation of colon cancer cells, and its anti-colon cancer mechanism may be related with the down-regulation of the expression levels of EGF,TGF-α,c-myc,ICAM-1and MMP2 proteins.