目的 研究槲皮素抗结肠癌细胞SW480生长的作用,并探索其可能的作用机制.方法 通过CCK-8法来检测SW480细胞在槲皮素处理下的增殖变化;运用HE染色、电镜观察和流式细胞术方法检测SW480细胞在槲皮素处理下的凋亡变化;运用Transwell检测槲皮素处理情况下SW480细胞在体外的粘附、运动和侵袭能力变化;运用明胶酶谱分析法检测槲皮素处理情况下SW480细胞基质金属蛋白酶分泌能力的变化.结果 CCK-8法检测显示槲皮素处理使SW480细胞受到了显著的增殖抑制,且具有剂量和时间依赖性;HE染色、流式细胞术及电镜分析发现槲皮素明显诱导细胞凋亡,并将SW480细胞周围阻滞于G2/M期;此外,槲皮素也能够使结肠癌SW480细胞的体外侵袭和运动能力受到抑制,且该抑制作用呈剂量依赖性关系;明胶酶谱法显示槲皮素处理后,SW480细胞对金属蛋白酶2(matrix metalloproteinase-2,MMP-2)和金属蛋白酶9(matrix metalloproteinase-9,MMP-9)的分泌均下降.结论 槲皮素对人结肠癌SW480细胞的增殖有明显的抑制作用,并能促进SW480细胞发生凋亡.槲皮素对结肠癌SW480细胞的迁移及侵袭能力均表现出抑制作用,并且呈剂量依赖性,这可能和槲皮素能够抑制MMP-2及MMP-9的分泌有关.

目的:探讨槲皮素(Que)调控5-氟尿嘧啶(5-FU)诱导的结直肠癌SW480细胞耐药及自噬的作用及机制.方法:采用浓度递增诱导法建立5-FU耐药细胞株SW480/5-FU,MTT法设置Que高、中、低剂量组(10、20、40μmol/L)和对照组.MTT法检测各组细胞的5-FU耐药性,TUNEL染色法检测细胞凋亡,免疫荧光检测细胞自噬活性,Western blot检测细胞p糖蛋白(Pgp)、多药耐药相关蛋白1(MRP1)、三磷酸腺苷结合转运蛋白G超家族成员2抗体(ABCG2)、LC3Ⅰ、LC3Ⅱ、p62、丝/苏氨酸激酶(AKT)、p-AKT、雷帕霉素靶蛋白(mTOR)和p-mTOR蛋白表达.结果:5-FU抑制SW480/5-FU细胞的半抑制浓度(IC50)明显高于SW480细胞(P<0.05),耐药指数(RI)=13.74.与对照组相比,Que中、高剂量组5-FU抑制SW480/5-FU细胞的IC50明显下降(P<0.05),耐药逆转倍数分别为2.27和4.03.与对照组相比,Que中、高剂量组细胞抑制率、凋亡率和自噬活性明显升高(均P<0.05),蛋白的表达均明显升高(均P<0.05),P-gp、MRP1、ABCG2、p62、p-AKT/AKT和p-mTOR/mTOR蛋白表达明显下降(均P<0.05).结论:Que可以以剂量依赖性的方式逆转SW480/5-FU细胞的5-FU耐药性,诱导细胞自噬,其作用机制可能与抑制AKT/mTOR的磷酸化有关.

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive ECpatients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/10(5), 94.62/10(5), 36.83/10(5) for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40-to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.