The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways.

Shufang Liang,Zifei Yin,Wanfu Lin,Ya’Ni Zhang,Qunwei Chen,Jingdong Gao,Juan Du,Yong Zou,Changquan Ling,Shu Li,Xiaolin Liu,Binbin Cheng

doi:10.1155/2018/5629304

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. In China, traditional Chinese herb medicine has been widely used in the treatment of HCC. Jiedu Recipe (JR) is a common used prescription which has shown good results against HCC. However, the exact mechanisms of JR are still unknown. Therefore, we investigated the efficacy of JR on HCC in the current study. JR inhibited the cell viability of both SMMC-7721 and Huh7 cells in both time- and dose-dependent manners. Transwell assay revealed that JR decreased the number of migrated cells of SMMC-7721 cells. JR treatment increased the E-cadherin expression level and decreased the levels of p-Smad2/3 and Smad2/3. Further study showed that JR reversed the effect of TGFβ1 on the expression of E-cadherin, vimentin, N-cadherin, and MMP2/9. JR also significantly inhibited TGFβ1-induced migration and invasion of SMMC-7721 and Huh7 cells determined by wound healing assay and transwell assay. TGFβ1 treatment increased the phosphorylation of Smad2/3, p38 MAPK, JNK, ERK1/2, and Akt in SMMC-7721 cells and pretreatment with JR blocked TGFβ1-induced activation of Smad2/3 and Akt and MAPKs. In conclusion, JR inhibits liver cancer cells migration and invasion through epithelial mesenchymal transition (EMT) inhibition via Smad2/3 dependent and independent pathways, suggesting it is an effective therapeutic strategy against HCC metastasis.

Highlights

Hepatocellular carcinoma (HCC), a leading cause of cancerassociated death, is one of the most common malignant tumors worldwide, especially in China
We showed that Jiedu Recipe (JR) exerts a surprising effect in preventing the metastasis or recurrence of HCC patients undergone tumor section
Our results showed that JR inhibited the proliferation, migration, and invasion of HCCs in vitro

Summary

Introduction

Hepatocellular carcinoma (HCC), a leading cause of cancerassociated death, is one of the most common malignant tumors worldwide, especially in China. The most common causes of mortality in HCC patients have been identified as cancer recurrence, metastasis, and deterioration of original tumors. Tumor resection is still the main therapeutic method for the treatment of HCC. Many patients are diagnosed at an advanced stage and thereby lost the operation chance. The high risk of metastasis is still the main cause for the treat failure and poor prognosis of HCC patients, even those with resectable small tumor [1]. Many new targeted drugs have been developed in recent years, such as sorafenib, the overall survival is not satisfactory [2]. The targeted drugs are usually too expensive for most of patients

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Conclusion