Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via Suppression: A Novel Therapeutic Strategy.

PURPOSE

Although chemotherapy is one of the standard treatments for gastric cancer, the disease's resistance mechanisms continue to limit the survival rates. (), an immune checkpoint belonging to the B7 family, is significantly overexpressed in gastric cancer. This work investigated the possibility of using suppression to improve the effectiveness of the widely used chemotherapy medication docetaxel.

MATERIALS AND METHODS

In this study, MKN-45 gastric cancer cells were transfected for 24 h with siRNA targeting , and then, docetaxel was added at optimal inhibitory doses (IC25 and IC50). To assess the impact of this combination therapy, cellular viability, proliferation, and migration were assessed using MTT assay, colony-forming unit assay, and wound-healing assay, respectively. Additionally, apoptosis and cell cycle status were evaluated by flow cytometry. Moreover, using qRT-PCR, the gene expression of and indicators associated with apoptosis was also examined.

RESULTS

The sensitivity of MKN-45 cells to docetaxel was greatly increased by the siRNA-mediated knockdown of , resulting in a decrease in the drug's IC50 value. When compared to each therapy alone, the combination of siRNA plus docetaxel at IC50 levels exhibited a significant increase in apoptosis rate. The volume of cells arrested at the sub-G1 and G2-M phase was shown to rise when siRNA transfection was combined with docetaxel. Furthermore, the combination treatment significantly decreased the ability of cells to migrate and form colonies.

CONCLUSIONS

suppression increases the susceptibility of MKN-45 gastric cancer cells to docetaxel treatment, resulting in decreased cellular proliferation and increased rates of apoptosis. The present work underscores the possibility of enhancing treatment results in gastric cancer by merging conventional chemotherapy with gene-silencing approaches.