Differentiation therapy of hepatocellular carcinoma by inhibiting the activity of AKT/GSK-3β/β-catenin axis and TGF-β induced EMT with sophocarpine
Authors: Pei-Qin Wang
Wei-Fen Xie
Jun-Ping Zhang
Chun-Ping Qiao
Xin Zhang
Fei Chen
Zhao-Shen Li
Yue-Xiang Chen
Qing Zhang
Ping-Ping Zhang
Zong-Li Yuan
Journal: Cancer Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: CSC; Differentiation; EpCAM; Hepatocellular carcinoma; Sophocarpine.
Affiliations: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China., Department of Gastroenterology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China., Department of Pharmacy, Second Military Medical University, Shanghai 200043, China., Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: .

Abstract:  Hepatocellular carcinoma progression is thought to be driven by cancer stem cells (CSCs). No clinical trial has, as yet, shown convincing long-term disease free survival results for the majority of patients in HCC. So it is important to discover new anti-cancer agents. In our study, we chose sophocarpine, which is derived from the foxtail-like sophora herb, for its efficacy to inhibit HCC including CSCs and potential mechanism study. Our results show that sophocarpine could not only reduce HCC cell viability, eliminate HCC and reverse hepatoma cells malignant phenotype, but also reduce the ratio of CSCs and inhibit the sphere formation of CSCs in vitro. In vivo, sophocarpine significantly displayed antitumor effects in subcutaneous xenograft HCC models and orthotopic transplantation tumor models. Further studies showed that sophocarpine could exert anti-tumor effects partly via downregulating the activity of the cancer stem cell related pathways and inhibiting EMT induced by TGF-β. 

Retracted: No

PubPeer comments:
 Manipulation in Figure 4 A and B: ![file] , 
 ![file] It might be caused by sections next to each other. Could the author show the original image in larger size? , 
 Thank you very much for your attention. As the first author of this article, I will explain your questions (Figure 4A) We examined several important signal pathways regulating tumor progression in LM3 cells, such as Ras MAPK, PI3K AKT and Wnt u03b2 catenin. The results showed that Akt pathway was down-regulated most obviously after sophocarpine treatment. (Figure 4B) We further detected the changes of downstream genes of AKT in LM3 cells treated with sophocarpine. In order to facilitate the understanding of the results, we present the results of the whole pathway completely, and put the upstream strip showed in figure 4A above the downstream strip again. Question 2. (Figure 6C) Here, continuous slices are used to detect CD90 and CD133 respectively. Because of the similar visual field selection, people mistakenly think that this is a different visual field of the same slice. Through simple magnification and comparison, we can find that there are obvious differences in similar visual fields. Thank you very much again, if you have any questions, please contact us without hesitate ,