Cheng Zhou, Xu Hui, Wang Xiaoping, Liu Zuoye
Department of Stomatology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Department of Stomatology, Yeda Hospital of Yantai, Yantai, Shandong 264006, P.R. China.
Exp Ther Med. 2017 Nov;14(5):4586-4594. doi: 10.3892/etm.2017.5105. Epub 2017 Sep 5.
The present study determined the ability of the GG strain (LGG) to enhance the anticancer effects of geniposide on HSC-3 human oral squamous carcinoma cells. LGG (1.0×10 CFU/ml) on its own had no impact on human oral keratinocytes and HSC-3 cancer cells. Geniposide (25 or 50 µg/ml) had no impact on human oral keratinocytes, but exerted growth inhibitory effects on HSC-3 cancer cells, which were increased in the presence of LGG. Flow cytometric analysis and a nuclear staining assay with DAPI revealed that HSC-3 cancer cells treated with LGG-geniposide (1.0×10 CFU/ml LGG and 50 µg/ml geniposide) had a higher apoptotic rate than cells in other treatment groups, particularly that treated with geniposide (50 µg/ml) only. Geniposide also increased the mRNA and protein expression of caspase-3, -8 and -9 as well as B-cell lymphoma 2 (Bcl-2)-associated X protein, p53, p21, inhibitor of nuclear factor-κB (NF-κB) α, Fas and Fas ligand, while decreasing Bcl-2, Bcl extra large protein, inhibitor of apoptosis-1 and -2, NF-κB, cyclooxigenase-2 and inducible nitric oxide synthase in HSC-3 cells, which was increased in the presence of LGG. These results indicated that LGG enhanced the anticancer effects of geniposide in HSC-3 cells.
本研究确定了鼠李糖乳杆菌GG株(LGG)增强京尼平苷对人HSC-3口腔鳞状癌细胞抗癌作用的能力。单独的LGG(1.0×10 CFU/ml)对人口腔角质形成细胞和HSC-3癌细胞没有影响。京尼平苷(25或50 µg/ml)对人口腔角质形成细胞没有影响,但对HSC-3癌细胞具有生长抑制作用,在LGG存在的情况下这种作用增强。流式细胞术分析和用4',6-二脒基-2-苯基吲哚(DAPI)进行的核染色分析显示,用LGG-京尼平苷(1.0×10 CFU/ml LGG和50 µg/ml京尼平苷)处理的HSC-3癌细胞比其他处理组的细胞具有更高的凋亡率,尤其是仅用京尼平苷(50 µg/ml)处理的细胞。京尼平苷还增加了半胱天冬酶-3、-8和-9以及B细胞淋巴瘤2(Bcl-2)相关X蛋白、p53、p21、核因子-κB(NF-κB)α抑制剂、Fas和Fas配体的mRNA和蛋白表达,同时降低了HSC-3细胞中Bcl-2、Bcl-2超大蛋白、凋亡抑制因子-1和-2、NF-κB、环氧化酶-2和诱导型一氧化氮合酶的表达,在LGG存在的情况下这种作用增强。这些结果表明,LGG增强了京尼平苷对HSC-3细胞的抗癌作用。