活血化瘀经典方剂对小鼠大肠癌肝转移模型端粒酶及p53、c-erbB-2、Bcl-2基因表达的影响

Expressions of hTERT, p53, c-erbB-2 and Bcl-2 in colonic adenocarcinoma mouse models with liver metastases: effects of classical traditional Chinese medicine prescriptions for promoting circulation and removing blood stasis

目的 观察活血化瘀方药对恶性肿瘤转移的影响并探讨其作用机制。方法 建立小鼠结肠癌CT-26细胞脾移植肝转移模型并应用活血化瘀代表方抵当汤、桂枝茯苓丸和丹参饮,观察实验组与对照组小鼠肝癌端粒酶、P53、C-erbB-2和Bcl-2蛋白的表达情况。结果 各组动物接种瘤细胞后均发生了不同程度的肿瘤转移情况。抵当汤、桂枝茯苓丸组与对病理对照组端粒酶、P53、C-erbB-2和Bcl-2蛋白的表达有显著性差异,丹参饮与病理对照组端粒酶的表达有显著性差异,但癌基因的表达没有显著性差异。结论 抵当汤和桂枝茯苓丸对大肠癌肝转移模型端粒酶和癌基因蛋白表达有抑制作用,丹参饮可抑制端粒酶的表达,对癌基因的表达没有抑制作用。这可能是活血化瘀方剂抑制肿瘤转移的机制之一,且活血化瘀的力度可能与抑制肿瘤转移的效果有关。

Objective To observe the effects of classical traditional Chinese medicine prescriptions that function to promote blood circulation and removing blood stasis on the metastatic behavior of malignant tumors, and explore the possible mechanisms of such effects. Methods BALB/c mouse models of colonic adenocarcinoma with liver metastases were established by intrasplenic injection of colonic adenocarcinoma cells (CT26) to receive treatment with the three representative classical circulation-promoting and blood stasis-removing prescriptions of traditional Chinese medicine, namely Guizhifuling pills, Didang Tang and Danshenyin, respectively. The expressions of human telomerase reverse transcriptase (hTERT), p53, c-erbB-2 and Bcl-2 were detected in the mouse models with different treatments and in normal control mice. Results Tumor metastases of various degrees were observed in the mice after inoculation of the tumor cells. The expressions of hTERT, p53, c-erbB-2 and Bcl-2 in the models receiving treatment with either Didang Tang or Guizhifuling pills differed significantly from those of the untreated model group (P<0.05), whereas between Danshenyin group and the model group, only the expression of hTERT showed significant difference. Conclusion Didang Tang and Guizhifuling pills can reduce the expressions of hTERT, p53, cerbB-2 and Bcl-2, while Danshenyin can only reduce the expression ofhTERT without similar effects on the other 3 oncogenes. Such inhibitory effects of the prescriptions on hTERT and the oncogenes might explain their actions to inhibit malignant tumor metastasis, which can be related to performance of the prescriptions in promoting circulation by removing blood stasis.