丹酚酸B通过Ctsk/STAT3轴对小鼠口腔癌的抑制作用
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国家自然科学基金(31400839)


Inhibitory effect of salvianolic acid B on oral cancer in mice by Ctsk/STAT3 axis
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    摘要:

    通过Ctsk/STAT3轴,探讨丹酚酸B对小鼠口腔癌的抑制作用。方法 随机将小鼠分为对照组、模型组、丹酚酸B低剂量组(10 mg·kg-1)、丹酚酸B高剂量组(40 mg·kg-1)、阳性药物组(4 mg·kg-1顺铂),每组20只。HE染色观察口腔颊囊黏膜组织,Brd U免疫组化法观察口腔黏膜细胞增殖指数,比较促炎因子IL-6、IL-1β、VEGF、HIF-1α水平,Ctsk、STAT3、SOCS3 mRNA以及Ctsk、STAT3、p-STAT3、SOCS3蛋白表达。结果 与对照组比较,模型组IL-6、IL-1β、VEGF、HIF-1α水平,Ctsk mRNA和蛋白、p-STAT3蛋白水平升高,SOCS3 mRNA和蛋白水平降低(P<0.05);与模型组比较,丹酚酸B低、高剂量组与阳性药物组SOCS3 mRNA和蛋白水平升高,单纯增生、轻度异常增生、重度异常增生、鳞癌病理程度及Brd U细胞增殖指数,IL-6、IL-1β、VEGF、HIF-1α水平,Ctsk mRNA和蛋白、p-STAT3蛋白水平降低(P<0.05);与丹酚酸B低剂量组比较,丹酚酸B高剂量组与阳性药物组SOCS3 mRNA与蛋白水平升高,单纯增生、轻度异常增生、重度异常增生、鳞癌病理程度及Brd U细胞增殖指数,IL-6、IL-1β、VEGF、HIF-1α水平,Ctsk mRNA和蛋白、p-STAT3蛋白水平降低(P<0.05);与丹酚酸B高剂量组比较,阳性药物组SOCS3 mRNA与蛋白水平升高,单纯增生、轻度异常增生、重度异常增生、鳞癌病理程度及Brd U细胞增殖指数,IL-6、IL-1β、VEGF、HIF-1α水平,Ctsk mRNA和蛋白、p-STAT3蛋白水平降低(P<0.05);HE结果显示,丹酚酸B低、高剂量组与阳性药物组口腔颊囊黏膜组织不同病理现象均较模型组出现改善,且丹酚酸B高剂量组与阳性药物组改善明显。结论 丹酚酸B对小鼠口腔癌具有抑制作用,可能通过调控Ctsk/STAT3轴相关mRNA和蛋白表达发挥作用

    Abstract:

    he inhibitory effect of salvianolic acid B on oral cancer in mice was studied by Ctsk/STAT3 axis. Methods Mice were randomly divided into control group, model group, salvianolic acid B low-dose group (10 mg·kg+1), salvianolic acid B high-dose group (40 mg·kg+1) and positive drug group (4 mg·kg+1 cisplatin), with 20 mice in each group. HE staining was used to observe oral cheek pouch mucosal tissue, Brd U immunohistochemical method was used to observe oral mucosal cell proliferation index, and the levels of pro-inflammatory factors IL-6, IL-1β, VEGF and HIF-1α were compared. Ctsk, STAT3, SOCS3 mRNA and Ctsk, STAT3, p-STAT3, SOCS3 protein expression were compared. Results Compared with control group, the levels of IL-6, IL-1β, VEGF and HIF-1α, Ctsk mRNA and protein, p-STAT3 protein and SOCS3 mRNA and protein were increased in model group (P<0.05). Compared with model group, SOCS3 mRNA and protein levels, pathological degree of simple hyperplasia, mild dysplasia, severe dysplasia, squamous cell carcinoma, Brd U cell proliferation index, IL-6, IL-1β, VEGF, HIF-1α levels in low and high dose salvianacid B groups and positive drug group were increased. The levels of Ctsk mRNA and protein and p-STAT3 protein were decreased (P<0.05). Compared with low-dose salvianolic acid B group, SOCS3 mRNA and protein levels, pathological degree of simple hyperplasia, mild dysplasia, severe dysplasia, squamous cell carcinoma, Brd U cell proliferation index, IL-6, IL-1β, VEGF, HIF-1α levels were increased in high-dose salvianolic acid B group and positive drug group. The levels of Ctsk mRNA and protein and p-STAT3 protein were decreased (P<0.05). Compared with salvianol B high-dose group, SOCS3 mRNA and protein levels, pathological degree of simple hyperplasia, mild dysplasia, severe dysplasia, squamous cell carcinoma, Brd U cell proliferation index, IL-6, IL-1β, VEGF, HIF-1α levels in positive drug group were increased. The levels of Ctsk mRNA and protein and p-STAT3 protein were decreased (P<0.05). HE results showed that different pathological phenomena of cheek pouch mucosa in low and high dose salvianolic acid B group and positive drug group were improved compared with model group, and the improvement was obvious in high dose salvianolic acid B group and positive drug group. Conclusion The inhibitory effect of salvianolic acid B on oral cancer in mice may be mediated by the expression of Ctsk/STAT3 axis related mRNA and protein.

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  • 在线发布日期: 2023-01-17
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