益气健脾化瘀方与5-Fu协同抑制胃癌转移的机制研究

Mechanism and Synergistic Inhibition of of Yiqi Jianpi Huayu Recipe and 5-Fu on Gastric Cancer Lung Metastasis

  • 摘要: 目的 观察益气健脾化瘀方协同5-氟尿嘧啶(5-Fu)对小鼠胃癌肺转移的抑制作用,并通过肿瘤相关巨噬细胞(Tumor-associated macrophages,TAMs)表型转化探讨其可能的作用机制。方法 30只615小鼠随机分为空白对照组、模型组、5-Fu组、益气健脾化瘀方(YQJPHY)组、5-Fu+益气健脾化瘀方(5-Fu+YQJPHY)组。除空白对照组外各组小鼠尾静脉注射MFC细胞建立小鼠胃癌肺转移模型。给药2周后取材,观察肿瘤浸润肺组织情况,计算肺转移抑制率,流式细胞术测定TAMs及M1、M2比例,免疫组化观察M2的表达,qPCR与Western blot检测N-cadherin、snail、slug的表达。结果 5-Fu+YQJPHY组肺转移灶结节及肿瘤浸润最少,抑制率最高(68.42%),明显高于其它组(P<0.05);较5-Fu组,5-Fu+YQJPHY组M1表达上升,M2表达明显下降,CD206表达减弱(P<0.05),N-cadharin、snail、slug表达水平最低(P<0.05)。结论 益气健脾化瘀方与5-Fu联用有明显的协同抑制小鼠胃癌肺转移瘤的效果,其机制可能与促进诱导M2型TAMs向M1型转变,从而抑制肿瘤细胞的上皮间质转化(EMT)有关。

     

    Abstract: OBJECTIVE To study the synergistic therapeutic effect of Yiqi Jianpi Huayu Recipe and 5-Fu on lung metastasis of gastric cancer in mice, and to elucidate the mechanism of tumor-associated macrophages (TAMs). METHODS 615 type mice were randomly divided into control group, model group, 5-Fu group, Yiqi Jianpi Huayu Recipe (YQJPHY) group, 5-Fu+ Yiqi Jianpi Huayu Recipe (5-Fu+YQJPHY) group. Except the control group, MFC cells were injected into the tail vein of each group to establish a mouse lung cancer metastasis model. After 2 weeks of administration, the tumor infiltrating lung tissues were observed, the lung metastasis inhibitory rates were calculated, TAMs and M1 and M2 ratios were determined by FCM, M2 expression was observed by immunohistochemistry, N-cadherin, snail and slug expression were detected by qPCR and Western blot. RESULTS In 5-Fu+YQJPHY group, the nodules and tumor infiltration were the least, and the inhibition rate was the highest (68.42%), which was significantly higher than that in the other groups (P<0.05). Compared with 5-Fu group, the expression of M1 significantly increased, the expression of M2 significantly decreased, the expression of CD206 was weaker (P<0.05). The expression of N-cadharin, snail and slug in 5-Fu+YQJPHY group was significantly lower than 5-Fu group (P<0.05). CONCLUSION Yiqi Jianpi Huayu Recipe combined with 5-Fu shows obvious synergistic effect on inhibiting lung metastasis of gastric cancer in mice. The mechanism may be related to the induction of M2-type TAMs to M1-type transformation, thereby inhibiting EMT of tumor cells.

     

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