Huaier Suppresses the Hepatocellular Carcinoma Cell Cycle by Regulating Minichromosome Maintenance Proteins

• Main Authors: Niu Y, Shan L, Gao H, Zhang C, Qian Z, Wang Z, Xu X, Zhang X, Wang J, Ma L, Chen L, Yu Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-11-01
• Series: OncoTargets and Therapy
• Subjects: mcm proteins; proteomics; cell cycle; huaier; hcc
• Online Access: https://www.dovepress.com/huaier-suppresses-the-hepatocellular-carcinoma-cell-cycle-by-regulatin-peer-reviewed-article-OTT

Yongjie Niu,1,* Liang Shan,2,* Han Gao,3 Congcong Zhang,1 Zijun Qian,1 Zhixian Wang,1 Xin Xu,4 Xiao Zhang,4 Jiayi Wang,4 Lifang Ma,1,4 Liyun Chen,5 Yongchun Yu1,4 1Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People’s Republic of China; 2Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China; 3Encephalopathy Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People’s Republic of China; 4Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China; 5Institute of Science, Technology and Humanities of Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyun ChenInstitute of Science, Technology and Humanities of Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road., Pudong New District, Shanghai 201203, People’s Republic of ChinaEmail [e-mail] YuShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, No. 274 Middle Zhijiang Road, Jingan District, Shanghai 200071, People’s Republic of ChinaEmail [e-mail]: Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment. Our previous studies demonstrated that Huaier enhanced chemotherapy sensitivity and restrained HCC proliferation. This study aimed to identify differentially expressed proteins with Huaier treatment in HCC cells, providing molecular targets for future targeted therapy of HCC.Materials and Methods: The effects of Huaier on the cell cycle were determined by flow cytometry and Western blot (WB). Xenograft models were used to verify the effects of Huaier on tumor growth. Then, proteomics was performed to identify the potential proteins regulated by Huaier. The enrichment analysis of GO and KEGG was performed for the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were used to detect the levels of proteins after Huaier treatment. After that the correlation of differentially expressed proteins with pathological stages was analyzed via the GEPIA database. We also analyzed candidate expression after Huaier treatment in HCC cells by WB and qRT-PCR. Furthermore, siRNA was performed to verify the targeted regulation of Huaier on candidate proteins.Results: First, the proteomics data showed that a total of 160 proteins were identified as differentially expressed proteins, among which six minichromosome maintenance (MCM) family members were enriched in the tumor-associated pathways after Huaier treatment. Moreover, MCM proteins were highly expressed in HCC and closely correlated with the survival of HCC patients. Finally, we confirmed that MCM proteins were targets of Huaier treatment in HCC cells.Conclusion: Huaier treatment was closely associated with the activation and inhibition of cancer-related pathways, and the MCM family was identified as a potential target in the antitumor process of Huaier. This study is helpful in understanding the molecular alterations and clinical relevance of HCC after Huaier treatment, which is beneficial for finding new targets and designing effective chemotherapy regimens for the future treatment of HCC.Keywords: MCM proteins, proteomics, cell cycle, Huaier, HCC