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Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate the effects of Pien Tze Huang (PZH) on the migration and invasion of HCC cells and underlying molecular mechanism.

Methods

Cell counting kit-8 (CCK-8) was applied to evaluate the cell viabilities of SMMC-7721, SK-Hep-1, C3A and HL-7702 (6 × 103 cells/well) co-incubated with different concentrations of PZH (0, 0.2, 0.4, 0.6, 0.8 mg/mL) for 24 h. Transwell, wound healing assay, CCK-8 and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration, invasion, proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells (650 µ g/mL for SK-Hep-1 cells and 330 µ g/mL for SMMC-7721 cells), respectively. In vivo, lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH. SK-Hep-1 cells (106 cells/200 µ L per mice) were injected into B-NDG mice via tail vein. Totally 8 mice were randomly divided into PZH and control groups, 4 mice in each group. After 2-d inoculation, mice in the PZH group were administered with PZH (250 mg/kg, daily) and mice in the control group received only vehicle (PBS) from the 2nd day after xenograft to day 17. Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to verify RNA-seq results. Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein (YAP).

Results

PZH treatment significantly inhibited the migration, invasion, proliferation and promoted the apoptosis of HCC cells in vitro and in vivo (P<0.01). Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH. Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta (PDGFRB), YAP, connective tissue growth factor (CCN2), N-cadherin, vimentin and matrix metallopeptidase 2 (MMP2, P<0.01). Meanwhile, the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo. Furthermore, PZH played roles in inhibiting the transcriptional activity of YAP.

Conclusion

PZH restrained migration, invasion and epithelial-mesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.

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Authors and Affiliations

  1. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China

    Zhi-yi Luo, Qi Tian, Niang-mei Cheng, Wen-han Liu, Ye Yang, Xiang-zhi Zhang, Xiao-yuan Zheng, Qiu-yu Zhuang, Bi-xing Zhao, Xiao-long Liu, Qin Li & Ying-chao Wang

  2. Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou Pien Tze Huang Pharmaceutical Co., Ltd., Zhangzhou, Fujian Province, 363099, China

    Zhi-yi Luo & Cong-sheng Liu

  3. College of Biological Science and Engineering and Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China

    Qi Tian, Niang-mei Cheng, Ye Yang, Xiang-zhi Zhang, Xiao-yuan Zheng, Qiu-yu Zhuang, Bi-xing Zhao, Xiao-long Liu, Qin Li & Ying-chao Wang

  4. Department of Internal Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China

    Wei Chen, Ming-sheng Chen & Qin Li

Authors
  1. Zhi-yi Luo
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  2. Qi Tian
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  6. Wei Chen
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Contributions

Tian Q and Cheng NM designed the experiments and drafted the manuscript. Luo ZY performed the analysis with constructive discussions and revised the manuscript. Yang Y, Liu WH, Chen W, Zhang XZ, Zhang XY and Zhuang QY carried out the experiments. Chen MS and Zhao BX contributed to the statistical analysis. Liu XL and Liu CS proofread the manuscript and provided technical support. Wang YC and Li Q designed and administrated the project, reviewed, and revised the manuscript.

Corresponding author

Correspondence to Qin Li.

Ethics declarations

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Luo ZY and Liu CS declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence this work. There is no professional of other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this paper.

Additional information

Supported by Joint Funds for Innovation of Science and Technology, Fujian Province (No. 2019Y9047), Joint Funds for Innovation of Science and Technology of Fujian Province (No. 2017Y9117), Young and Middle-Aged Talent Training Project of Fujian Provincial Health and Family Planning Commission (No. 2020GGA072), Natural Science Foundation of Fujian Province (No. 2020J011164, 2020J011170), Startup Fund for Scientific Research, Fujian Medical University (No. 2019QH1298), Science and Technology Plan Project of Fuzhou (No.2019-S-87) 1.

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Luo, Zy., Tian, Q., Cheng, Nm. et al. Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity. Chin. J. Integr. Med. 30, 115–124 (2024). https://doi.org/10.1007/s11655-022-3533-8

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