云芝糖肽通过调控p-糖蛋白 提高多柔比星胃癌细胞毒性的作用和机制研究

目的：探讨云芝糖肽辅助化疗药多柔比星协同增效的机制。方法：CCK-8检测云芝糖肽影响多柔比星在AGS胃癌细胞中细胞毒性的作用；LC-MS/MS法检测云芝糖肽对多柔比星在AGS细胞内累积的影响；RT-PCR检测云芝糖肽对AGS细胞P-gp的mRNA表达的影响；流式细胞术检测云芝糖肽对AGS细胞表面P-gp蛋白表达的影响。结果：云芝糖肽能显著增加多柔比星对AGS胃癌细胞的毒性；中、高浓度（0.5、1.0 mg·mL-1）的云芝糖肽显著增加多柔比星在AGS胃癌细胞内的累积；中、高浓度（0.5、1.0 mg·mL-1）的云芝糖肽显著减少AGS胃癌细胞p-gp mRNA的表达，显著减少AGS胃癌细胞表面P-gp蛋白的表达。结论：云芝糖肽能提高多柔比星在AGS细胞上的药效，其机制可能与减少细胞P-gp表达有关，减少了多柔比星在肿瘤细胞的外排，增加胞内浓度，从而提高药效。

Effect and Mechanism of Polysaccharopeptides from Coriolus Versicolor in Enhancing Doxorubicin Cytotoxicity in Gastric Cancer Cells by Regulating P-glycoprotein Expression

Objective: A new mechanism for the synergistic effect of polysaccharopeptides from coriolus versicolor in chemotherapy with doxorubicin from a drug-drug interaction perspective. Methods: CCK-8 was used to detect the effect of polysaccharopeptides on the cytotoxicity of doxorubicin in AGS gastric cancer cells. LC-MS/MS was used to detect the effect of polysaccharopeptides on the accumulation of doxorubicin in AGS cells. RT-PCR was used to detect the effect of polysaccharopeptides on the mRNA expression of P-gp in AGS cells. Flow cytometry was used to detect the effect of polysaccharopeptides on the protein expression of P-gp on the surface of AGS cells. Results: Polysaccharopeptides significantly increased the toxicity of doxorubicin on AGS gastric cancer cells. The accumulation of doxorubicin in AGS gastric cancer cells was significantly increased by medium and high concentrations (0.5 and 1.0 mg·mL-1) of polysaccharopeptides. Medium and high concentrations of polysaccharopeptides (0.5 and 1.0 mg·mL-1) significantly decreased the mRNA expression of P-gp in AGS gastric cancer cells, as well as the protein expression of P-gp on the surface of AGS gastric cancer cells. Conclusion: Polysaccharopeptides enhance the efficacy of doxorubicin on AGS cells, and the mechanism may be related to the reduction of cellular P-gp expression, which reduces the drug efflux of doxorubicin in tumor cells and increases the intracellular concentration, thus increasing the efficacy.