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, Yong Zou, Jingdong Gao, Xiaolin Liu, Wanfu Lin, Zifei Yin, Juan Du, Ya'ni Zhang, Qunwei Chen, Shu Li, Binbin Cheng, Changquan Ling
Author Information
  1. Shufang Liang: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. ORCID
  2. Yong Zou: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. ORCID
  3. Jingdong Gao: Department of Oncology, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215009, China.
  4. Xiaolin Liu: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
  5. Wanfu Lin: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. ORCID
  6. Zifei Yin: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
  7. Juan Du: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. ORCID
  8. Ya'ni Zhang: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
  9. Qunwei Chen: Department of Oncology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang 310006, China. ORCID
  10. Shu Li: Department of Gastroenterology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201900, China.
  11. Binbin Cheng: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. ORCID
  12. Changquan Ling: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. ORCID

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 TGF1 on the expression of E-cadherin, vimentin, N-cadherin, and MMP2/9. JR also significantly inhibited TGF1-induced migration and invasion of SMMC-7721 and Huh7 cells determined by wound healing assay and transwell assay. TGF1 treatment increased the phosphorylation of Smad2/3, p38 MAPK, JNK, ERK1/2, and Akt in SMMC-7721 cells and pretreatment with JR blocked TGF1-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.

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Word Cloud

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