Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway
Ruoyu Wang 1 , Dong Zhang 2 , Kewei Sun 1 , Jianping Peng 1 , Wenfang Zhu 1 , Sihan Yin 1 , Dan Tang 1 , Yunan Wu 3
Affiliations
Affiliations
1
Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
2
Department of Hepatology, Guangdong Hospital of Traditional Chinese Medicine in Zhuhai, Zhuhai, 519015, Guangdong, China.
3
Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China. [email protected].
PMID: 33435880 DOI: 10.1186/s12879-020-05713-0
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Abstract
Background: Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression.
Methods: The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays.
Results: We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment.
Conclusion: Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.
Keywords: Amygdalin; Hepatitis B virus (HBV); Hepatocellular carcinoma (HCC); T cell; The JAK2/STAT3 signaling. 作者: StephenW 时间: 2021-1-15 13:26