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目的研究化瘀丸(HYW)对4T1乳腺癌荷瘤小鼠乳垫原位瘤和转移瘤的抑制作用,对瘤组织和血小板肝素酶(heparanase 1,HPSE)表达的影响,及对肿瘤相关生长因子VEGF,PDGF和b FGF表达的影响。方法采用Balb/c小鼠乳垫原位注射4T1-luc2细胞悬液的方法制成乳腺癌原位移植瘤模型。实验分为模型组、化瘀丸高剂量组(HYWH),化瘀丸低剂量组(HYW-L),给药4周后观察化瘀丸对小鼠原位移植瘤体积、瘤重以及抑瘤率,给药6周后观察药物对转移瘤光子数的影响。通过Western blotting蛋白印迹法检测化瘀丸对瘤组织肝素酶(HPSE)表达的影响。通过免疫组化的方法检测化瘀丸对移植瘤VEGF,PDGF和b FGF表达的影响。结果给药4周后与模型组相比,HYW-H和HYW-L组小鼠乳垫原位瘤生长曲线均有所减小,瘤重从模型组的1.048 g分别下降到0.814和0.835 g(P<0.05),抑瘤率分别为22%和20%。给药6周后与模型组相比,HYW-H和HYW-L组小鼠胸部转移瘤光子数均明显下降,其中HYW-H组下降具有统计学差异(P<0.05)。Western蛋白印迹法检测结果显示,与模型组相比,药物干预后肿瘤组织和血小板肝素酶表达均有所下降,其中肝素酶表达下降与药物浓度成正比。免疫组化结果显示,化瘀丸治疗后瘤组织VEGF,PDGF和b FGF的表达均有所下降。结论化瘀丸能抑制4T1乳腺癌荷瘤小鼠乳垫原位瘤和转移瘤,其机制可能与化瘀丸降低了肿瘤转移相关蛋白肝素酶及肿瘤相关生长因子VEGF,PDGF和b FGF。
Objective To study the effect of Huyu pill (HYW) on the expression of heparanase 1 (HPSE) in breast tumor and metastatic tumor of 4T1 breast cancer-bearing mice and its correlation with tumor Effects of growth factors VEGF, PDGF and b FGF expression. Methods In situ injection of 4T1-luc2 cell suspension into Balb / c mice was used to prepare orthotopic breast cancer model. The experimental group was divided into model group, high-dose Huayu Wan group (HYWH) and low-dose Huayu Pills group (HYW-L). After 4 weeks of administration, the effects of Huayu Pills on the tumor volume, The tumor rate, after 6 weeks of administration observed the impact of drugs on the number of metastases photons. The effect of Huayu Pill on the expression of heparanase (HPSE) in tumor tissue was detected by Western blotting and Western blotting. The effect of Huayu Pill on the expression of VEGF, PDGF and b FGF was examined by immunohistochemistry. Results Compared with the model group, the growth curve of mammary glands in situ in HYW-H and HYW-L groups decreased after 4 weeks and the tumor weight decreased from 1.048 g to 0.814 and 0.835 g (P <0.05). The tumor inhibition rates were 22% and 20% respectively. Compared with the model group, the number of photons in the chest metastases of HYW-H and HYW-L groups decreased significantly after 6 weeks of administration, and the difference was statistically significant (P <0.05) in HYW-H group. Western blotting results showed that compared with the model group, the expression of tumor tissue and platelet heparanase decreased after drug intervention, and the decrease of heparanase expression was proportional to the drug concentration. The results of immunohistochemistry showed that the expression of VEGF, PDGF and b FGF in the tumor tissue of Huayu Pill decreased. Conclusion Huayu Pills can inhibit the in situ mammary gland tumor and metastasis of 4T1 breast cancer-bearing mice. The mechanism may be that Huayu Pill can reduce the tumor-associated protein heparinase and tumor-associated growth factor VEGF, PDGF and b FGF.