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中药健脾化瘀汤通过调节Smad3/Smad7级联反应抑制上皮-间质转化。

The Chinese medicine, Jianpi Huayu Decoction, inhibits the epithelial mesenchymal transition via the regulation of the Smad3/Smad7 cascade.

作者信息

Zhong Chong, Zhang Yong-Fa, Huang Jun-Hai, Wang Zi-Yu, Chen Qiu-Yuan, Su Li-Tian, Liu Zhen-Tao, Xiong Cheng-Ming, Tao Zhi, Guo Rong-Ping

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405, China.

Department of Hepatobiliary Oncology, Cancer Center of Sun Yat-sen UniversityGuangzhou 510060, China.

出版信息

Am J Transl Res. 2017 Jun 15;9(6):2694-2711. eCollection 2017.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors in the world. In China, traditional medicine is commonly used in the treatment of cancer. Among these medicines, Jianpi Huayu Decoction (JHD) is a typical clinical prescription against multiple tumors. However, the exact function and targets of JHD are currently unknown. The aim of this study is to assess the efficacy of JHD against HCC.

METHODS AND RESULTS

Hepatic carcinoma SMMC7221 cells were treated with JHD drug-serum in a dose- and time-dependent manner. Real-time PCR (RT-PCR), western-blot (WB), and immunofluorescence microscopy revealed that JHD increased both the mRNA and protein levels of Smad7 and decreased the protein level of p-Smad3. It subsequently increased the E-cadherin expression level and decreased those of N-cadherin and Vimentin. Metastasis and invasion were eventually inhibited, as determined by the wound healing and transwell invasion assays. Treatment of Tanshinone IIA (Tan IIA) showed similar results as JHD, indicating that it is most likely the main functional drug monomer of JHD. The assay in nude mice also revealed the efficacy of JHD to inhibit epithelial mesenchymal transition (EMT).

CONCLUSION

JHD was shown to be an effective therapeutic strategy against HCC.

摘要

背景

肝细胞癌(HCC)是世界上最常见且侵袭性最强的恶性肿瘤之一。在中国,传统医学常用于癌症治疗。在这些药物中,健脾化瘀汤(JHD)是一种针对多种肿瘤的典型临床方剂。然而,JHD的确切作用和靶点目前尚不清楚。本研究的目的是评估JHD对HCC的疗效。

方法与结果

用JHD含药血清以剂量和时间依赖性方式处理肝癌SMMC7221细胞。实时荧光定量聚合酶链反应(RT-PCR)、蛋白质免疫印迹法(WB)和免疫荧光显微镜检查显示,JHD增加了Smad7的mRNA和蛋白质水平,并降低了p-Smad3的蛋白质水平。随后它增加了E-钙黏蛋白的表达水平,并降低了N-钙黏蛋白和波形蛋白的表达水平。通过伤口愈合和Transwell侵袭试验确定,转移和侵袭最终受到抑制。丹参酮IIA(Tan IIA)的处理显示出与JHD相似的结果,表明它很可能是JHD的主要功能性药物单体。裸鼠实验也揭示了JHD抑制上皮-间质转化(EMT)的疗效。

结论

JHD被证明是一种治疗HCC的有效策略。

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Hepatocellular carcinoma.肝细胞癌。
Nat Rev Dis Primers. 2016 Apr 14;2:16018. doi: 10.1038/nrdp.2016.18.
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Cancer statistics in China, 2015.《中国癌症统计数据 2015》
CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.
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Regulation of EMT by TGFβ in cancer.TGFβ 对 EMT 的调控在癌症中的作用。
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