茄碱通过 MICA 的 DNA 去甲基化恢复胃癌对 NK 细胞的敏感性

Solasonine, extracted from Solanum nigrum, has been proven to exert anti-tumor effects in various tumors.

However, the role of solasonine in gastric cancer remains unclear.

This study aims to elucidate the therapeutic effects of solasonine in suppressing gastric cancer progression.

This study explores the regulatory mechanism of solasonine in vitro cells and xenograft tumor mouse models. Methylation-specific PCR (MSP) is used for DNA methylation analysis; immunohistochemical and flow cytometry are performed for MHC class I polypeptide-related sequence A (MICA) expression profiling. Solasonine inhibits the proliferation and migration of gastric cancer cells. MICA is identified as a regulatory target for solasonine in gastric cancer cells.

Mechanistically, DNA methylation of MICA is suppressed by solasonine. DNA methyltransferases (DNMT) family members, DNMT1, DNMT3A, and DNMT3B, are downregulated in solasonine-treated tumor tissues.

Importantly, solasonine restores the sensitivity of HGC-27 cells to natural killer (NK) cells through upregulating MICA, suggesting the potential value of solasonine as an immunotherapy drug in gastric cancer. Solasonine inhibits gastric cancer progression and restores sensitivity of gastric cancer to NK cells through inducing DNA demethylation of the MICA promoter in vitro and in vivo.

This study provides application prospects for solasonine anti-tumor therapy.