基于糖尿病-肿瘤小鼠模型研究糖尿病对结直肠癌/乳腺癌进展及肠道菌群的影响

Effects of Diabetes on Colorectal Cancer/Breast Cancer Progression and Intestinal Flora Based on a Diabetes-tumor Mouse Model

目的通过构建糖尿病-肿瘤小鼠模型,对不同处理组小鼠体质量、肿瘤体积、生存率,以及肠道菌群数据进行统计分析,探讨糖尿病对肿瘤进展的影响,以及糖尿病合并结直肠癌或乳腺癌对肠道菌群的影响。方法60只小鼠分为空白对照组、糖尿病组、结直肠癌组、乳腺癌组、糖尿病+结直肠癌组、糖尿病+乳腺癌组。通过链脲佐菌素注射建立糖尿病小鼠模型,在此基础上进一步建立结直肠癌和乳腺癌的实体瘤模型。观察记录各组小鼠的体质量、肿瘤体积变化,计算生存率。采集小鼠粪便,然后利用QIIME2平台基于DATA2和Vesearch方法对粪便中微生物群落测序数据进行分析。结果糖尿病合并结直肠癌或者乳腺癌后,小鼠体质量(P<0.05)和生存率(P<0.01)均明显降低,但小鼠肿瘤体积无明显变化。与空白对照组、糖尿病组或结直肠癌组相比,糖尿病+结直肠癌组小鼠肠道菌群的alpha多样性明显改变(P<0.05),而糖尿病合并乳腺癌并未引起肠道菌群的alpha多样性产生变化(P>0.05);同时,糖尿病合并结直肠癌或乳腺癌对小鼠肠道菌群的beta多样性和细菌物种组成也产生一定影响。结论糖尿病会促进结直肠癌或乳腺癌的进展。糖尿病合并结直肠癌或乳腺癌对小鼠肠道菌群的影响比单独结直肠癌或单独乳腺癌的影响更大。

Objective To investigate the effects of diabetes on tumor progression,and the effects of diabetes combined with colorectal or breast cancer on the intestinal flora by constructing a diabetes-tumor mouse model,and the differences in body mass,tumor volume,survival rate,and initial flora of the mice in different treatment groups were statistically analyzed.Methods Sixty mice were divided into control,diabetes,colorectal cancer,diabetes+colorectal cancer,breast cancer,and diabetes+breast cancer groups.The diabetic mouse model was established by streptozotocin injection,and solid tumor models of colorectal and breast cancer were further established on this basis.Changes in the body mass,tumor volume,and survival rate of the mice in each group were observed and analyzed.The mouse feces were collected,and then the microbial community sequencing data were analyzed using the QIIME2 platform based on the DATA2 and Vesearch methods.Results The body mass(P<0.05)and survival rate(P<0.01)of mice with diabetes combined with colorectal or breast cancer were significantly reduced,but there was no significant difference in tumor volume in mice.Compared with the control group or the colorectal cancer group,the species richness of the intestinal flora in mice in the diabetes+colorectal cancer group was significantly altered(P<0.05);while the diabetes+breast cancer group did not significantly change(P>0.05).The beta diversity and bacterial species composition of the intestinal flora in mice with diabetes combined with colorectal or breast cancer were also affected.Conclusion Diabetes promotes the progression of colorectal or breast cancer.Diabetes combined with colorectal or breast cancer has a greater impact on the intestinal flora of mice than colorectal or breast cancer alone.