结直肠癌(CRC)构成了重大的全球健康负担,是全球第三大流行癌症,也是导致癌症相关死亡的第二大因素。预防策略对于应对这种上升的发病率至关重要。6-shogaol,源自生姜,在预防和治疗各种癌症方面显示出了希望。本研究研究了6-shogaol对偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)诱导的小鼠CRC的预防作用。40只雄性BALB/c小鼠随机分为对照组,6-shogaol,AOM+DSS,和6-shogaol+AOM+DSS。对照组小鼠接受玉米油16周,而6-shogaol组给予20mg/kg的6-shogaol,持续16周。AOM+DSS组接受单次腹膜内剂量(ip)10mg/kg的AOM,其次是在饮用水中进行3个周期的2.5%DSS。6-shogaol+AOM+DSS组同时接受6-shogaol治疗16周,单次ip10mg/kgAOM,其次是在饮用水中进行3个周期的2.5%DSS。AOM+DSS处理的小鼠表现出食物消耗减少,结肠重量,和结肠长度,随着肿瘤形成的增加。6-shogaol的共同管理有效地扭转了这些变化,抑制CRC发展。组织病理学分析显示6-shogaol对结肠损伤和炎症反应调节的保护作用。6-shogaol显着降低癌胚抗原和Kiel67水平,表明抑制肿瘤细胞增殖。机械上,6-shogaol通过上调蛋白53和caspase-3表达促进细胞凋亡,通过调节β-catenin和腺瘤性结肠息肉病水平,有效恢复无翼相关整合位点信号通路的平衡。此外,6-shogaol表现出抗炎作用,减少髓过氧化物酶,肿瘤坏死因子α,和环加氧酶-2在AOM/DSS处理的小鼠中的水平。此外,6-shogaol通过减少脂质过氧化和亚硝化应激并增强抗氧化酶活性来恢复氧化还原稳态。研究结果表明,6-shogaol抑制细胞增殖,诱导细胞凋亡,调节Wnt信号,抑制炎症,并恢复氧化还原稳态,全面了解其对CRC的潜在治疗益处。
Colorectal cancer (CRC) poses a significant global health burden, being the third most prevalent cancer and the second most significant contributor to cancer-related deaths worldwide. Preventive strategies are crucial to combat this rising incidence. 6-shogaol, derived from ginger, has shown promise in preventing and treating various cancers. This study investigated the preventive effects of 6-shogaol on azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC in mice. Forty male BALB/c mice were randomly divided into control, 6-shogaol, AOM + DSS, and 6-shogaol + AOM + DSS. Mice in the control group received corn oil for 16 weeks, while those in the 6-Shogaol group were administered 20 mg/kg of 6-shogaol for 16 weeks. The AOM + DSS group received a single intraperitoneal dose (ip) of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The 6-shogaol + AOM + DSS group received both 6-shogaol for 16 weeks and a single ip of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The AOM + DSS-treated mice exhibited reduced food consumption, colon weight, and colon length, along with increased tumor formation. Co-administration of 6-shogaol effectively reversed these changes, inhibiting CRC development. Histopathological analysis revealed protective effects of 6-shogaol against colonic insults and modulation of inflammatory responses. 6-shogaol significantly reduced Carcinoembryonic antigen and Kiel 67 levels, indicating inhibition of tumor cell proliferation. Mechanistically, 6-shogaol promoted apoptosis by upregulating protein 53 and caspase-3 expression, and it effectively restored the balance of the Wingless-related integration site signaling pathway by regulating β-catenin and adenomatous polyposis coli levels. Moreover, 6-shogaol demonstrated anti-inflammatory effects, reducing myeloperoxidase, Tumor necrosis factor alpha, and cyclooxygenase-2 levels in AOM/DSS-treated mice. Additionally, 6-shogaol restored redox homeostasis by reducing lipid peroxidation and nitrosative stress and enhancing antioxidant enzyme activities. The findings suggest that 6-shogaol inhibits cell proliferation, induces apoptosis, regulates Wnt signaling, suppresses inflammation, and restores redox homeostasis, providing comprehensive insights into its potential therapeutic benefits for CRC.