Solanine Inhibits Immune Escape Mediated by Hepatoma Treg Cells via the TGFβ/Smad Signaling Pathway

• Published in: BioMed research international 2020, Vol.2020 (2020), p.1-10
• Main Authors: Cui, Yiyi, Wang, Jue, Ying, Yinyin, Gao, Juwei
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animal tissues; Animals; Antibodies; Antigens; Antineoplastic Agents - pharmacology; Antitumor activity; Bioengineering; Blood; Breast cancer; Carbon dioxide; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; CD25 antigen; CD4 antigen; Cell culture; Cell cycle; Cell growth; Cytokines; Female; Flow cytometry; Fluorescence; Foxp3 protein; Hepatocellular carcinoma; Hepatoma; Humans; Immune evasion; Immune response; Immune system; Immunoregulation; Immunotherapy; Inhibitors; Interleukin 10; Interleukin 2; Laboratory animals; Liver; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Lymphocytes; Lymphocytes T; Metastases; Metastasis; Mice, Nude; Middle Aged; Peripheral blood; Signal transduction; Signal Transduction - drug effects; Smad protein; Smad Proteins - metabolism; Solanine - pharmacology; Spleen; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Thymus gland; Transforming Growth Factor beta - blood; Transforming Growth Factor beta - metabolism; Tumor Escape - drug effects; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumors; Xenograft Model Antitumor Assays
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2020/9749631

Objective. To observe the inhibitory effect of solanine on regulatory T cells (Treg) in transplanted hepatoma mice and to study the mechanism of solanine inhibiting tumor growth. Methods. The levels of Treg cells and IL-2, IL-10, and TGFβ in the blood of patients with liver cancer were detected by flow cytometry and ELISA, respectively. A mouse hepatocellular carcinoma (HCC) graft model was established and randomly divided into four groups: control group, solanine group, TGFβ inhibitor group (SB-431542), and solanine +TGFβ inhibitor combined group. Tumor volume of each group was recorded, tumor inhibition rate was calculated, and tumor metastasis was counted. The proportion of CD4+CD25+Foxp3+ Treg in transplanted tumor tissues was detected by flow cytometry. The expression levels of Foxp3 and TGFβ in transplanted tumor tissues were detected by quantitative fluorescence PCR. Results. Compared with healthy people, Treg cells and IL-2, IL-10, and TGFβ contents in peripheral blood of liver cancer patients were increased. The results of the transplanted tumor model in mice showed that the tumor volume of the transplanted mice in the solanine group and the TGFβ inhibitor mice was reduced compared with the control group. The combined group had the smallest tumor volume. The proportion of CD4+CD25+Foxp3+ Treg in the transplanted tumor tissues of mice in the solanine treatment group was significantly lower than that in the control group. The expressions of Foxp3 and TGFβ in the transplanted tumor tissues of mice in the solanine group were significantly lower than those in the control group. Conclusion. Solanine may enhance the antitumor immune response by downregulating the proportion of CD4+CD25+ Treg and the expression of Foxp3 and TGFβ in tumor tissues.