【摘要】 目的 探讨香菇多糖（LTN）联合紫杉醇对乳腺癌细胞的生物学功能和作用机制。方法 将MCF-10A细胞、MDA-MB-231细胞和MCF-7细胞随机分为对照组、LTN组、紫杉醇组和联合组。采用四甲基噻唑蓝法检测细胞存活率，伤口愈合实验和Transwell分别检测乳腺癌细胞迁移、侵袭能力，实时荧光定量聚合酶链反应测定FGFR1和FGFR2的mRNA表达，Western blotting法检测FGF1和FGFR1蛋白表达水平。使用GEO数据库分析FGFR1和FGFR2的表达对乳腺癌患者总生存期和无病生存期的影响。结果 1 000μg/mL的LTN与20 nmol/L紫杉醇联合处理时，对正常乳腺上皮细胞的抑制作用最低。与对照组相比，LTN组、紫杉醇组和联合组MDA-MB-231细胞迁移和侵袭能力均下降，联合组MCF-7细胞迁移能力下降（P <0.001）。与对照组相比，联合组MDA-MB-231细胞的FGFR1 mRNA表达，LTN组和联合组MDA-MB-231细胞的FGFR2 mRNA表达均显著下降（P <0.05）。与对照组相比，LTN组和联合组MDA-MB-231细胞FGF1蛋白表达下降，各处理组MDA-MB-231细胞FGFR1蛋白表达下降。GEO数据库中，FGFR1和FGFR2在低表达水平时总生存期和无病生存期提高（P <0.05）。结论 LTN可降低紫杉醇对正常乳腺上皮细胞的毒性作用，亦可增强紫杉醇对乳腺癌细胞增殖、迁移和侵袭能力的抑制作用。低表达水平FGFR1和FGFR2具有良好的预后效果，LTN和紫杉醇联合用药可能下调MDA-MB-231细胞FGF1/FGFR1基因表达，达到抑制三阴乳腺癌作用。更多还原

【Abstract】 Objective To investigate the biological function of lentinan(LTN) in combination with taxol in breast cancer cell proliferation and its drug resistance and feasibility in clinical use. Methods MCF-10A cells,MDA-MB-231 cells and MCF-7 cells were randomly divided into a control, LTN, taxol and combined groups.Cell survival was detected by MTT assay, breast cancer cell migration and invasion levels detected by WoundHealing Assay and Transwell, respectively; FGFR1 and FGFR2 mRNA expression was determined by realtime fluorescence quantitative PCR, and FGF1 and FGFR1 protein expression levels detected by Western blotting. The effects of FGFR1 and FGFR2 expression on the overall survival and disease-free survival of breast cancer patients were further analyzed using the GEO database. Results The lowest inhibitory effect on normal breast epithelial cells was observed when 1 000 μg/mL of LTN was co-treated with 20 nmol/L taxol. Compared with the control, the migration and invasion ability of MDA-MB-231 cells in the LTN group, taxol group, and combined group, and the migration ability of MCF-7 cells in the combined group were significantly decreased(P < 0.001). Compared with the control group, the FGFR1 mRNA expression of MDA-MB-231 cells in the combined group, and the FGFR2 mRNA expression of MDAMB-231 cells in the LTN group and combined group were significantly decreased(P < 0.05). Compared with the control group, FGF1protein expression was decreased in MDA-MB-231 cells in the LTN group and combined group, and FGFR1protein expression decreased in MDA-MB-231 cells in each treatment group. In the GEO database, FGFR1and FGFR2 showed improved overall survival and disease-free survival at low expression levels(P < 0.05).Conclusion LTN can reduce the toxic effects of taxol on normal breast epithelial cells, and can also enhance the inhibitory effects of taxol on the proliferation, migration and invasion ability of breast cancer cells. Low expression levels of FGFR1 and FGFR2 have good prognostic effects, and the combination of LTN and taxol may down-regulate the expression of FGF1/FGFR1 genes in MDA-MB-231 cells to achieve the anti-triplenegative breast cancer effect.更多还原