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

Abstract

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.

Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways

“…It can exert anticancer effects by inhibiting cell proliferation, inducing apoptosis, blocking the cell cycle, inducing autophagy, enhancing chemoradiation, inhibiting epithelial–mesenchymal transformation, inhibiting tumor metastasis, and inhibiting angiogenesis, such as in liver cancer, breast cancer, liver cancer, pancreatic cancer, and colorectal cancer [ 183 ]. Studies have shown that serine inhibits the growth of transplanted hepatocellular carcinoma (HCC) in mice and reduces the CD4 + CD25 + Foxp3 + proportion of Treg and the expression levels of Foxp3 and TGFβ mRNA, and enhanced the body’s antitumor immune response by inhibiting the TGF/SMAD signaling pathway [ 184 ]. Furthermore, it reduced the expression and activity of Akt and ER, and this inhibitory effect may contribute to inactivated PI3K/Akt and ER signaling pathways in human endometrial cancer cells [ 185 ].…”

A narrative review of the antitumor studies of solanine

“…Tumor immune escape refers to the phenomenon in which tumor cells escape recognition and attack by the body’s immune system through a variety of mechanisms, so as to survive and proliferate in the body. It is reported that 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 ( 35 ).…”

The pathogenesis of liver cancer and the therapeutic potential of bioactive substances

“…Solanine is a steroidal alkaloid extracted from Solanum tuberosum Linn. Studies have found that solanine can enhance the anti-tumor immune response by down-regulating CD4 + CD25 + Tregs in tumor tissue and down-regulating the expression of Foxp3 and TGF-β ( Gao et al, 2020 ).…”