右旋柠檬烯对双酚A影响下人源乳腺癌MDA-MB-231裸鼠移植瘤生长及肠道菌群的影响

Effects of D-limonene on Proteomics and IntestinalMicrobial Diversity of Breast Cancer MDA-MB-231Nude Mice in Bisphenol A Environment

观察右旋柠檬烯对环境雌激素双酚A影响下荷人源MDA-MB-231乳腺癌裸小鼠移植瘤的抑制情况和肠道菌群的影响。将人源乳腺癌MDA-MB-231细胞接种于Balb/c-nu/nu雌性裸鼠右侧腋窝皮下建立人三阴性乳腺癌裸鼠移植瘤模型,获得的30只三阴性乳腺癌荷瘤裸鼠随机分为5组,模型组(每天予蒸馏水),双酚A+右旋柠檬烯低、中、高剂量组(0.25 mL/kg、0.5 mL/kg、1 mL/kg),双酚A组(1 mL/kg),每组6只;每天灌胃给药1次,连续6周。实验结束,观察比较右旋柠檬烯低、中、高剂量组与模型组荷瘤鼠肿瘤质量、瘤体体积的变化,计算肿瘤抑制率,采用高通量测序技术检测荷瘤小鼠的肠道菌群变化。结果:双酚A组肿瘤较对照肿瘤组肿瘤增加大,双酚A+右旋柠檬烯低、中、高剂量组中的乳腺癌肿瘤体积、瘤重比对照组和双酚A组减小;接种肿瘤后细菌种类和丰度下降,右旋柠檬烯治疗后肠道菌群种类和丰度增加,右旋柠檬烯中高剂量组疣微菌门菌verrucomicrobiota丰度较双酚A组和对照组的明显增多,而拟杆菌门Bacteroidet丰度较双酚A组和对照组的明显减少。在属水平上,与对照组相比,双酚A及右旋柠檬烯处理组拟杆菌属Bacteroides、异戊酸杆菌Alloprevotella、阿克曼氏菌Akkermansia、乳杆菌Lactobacillus、螺杆菌属Helicobacter、毛螺旋菌属Parasutterella差异较大,但未达到显著性意义。结论:右旋柠檬烯对双酚A条件下的乳腺癌增殖有一定的抑制作用,并影响了双酚A环境下的三阴性乳腺癌裸鼠肠道菌群的数量和丰度。

To observe the effect of D-Limonene on breast cancer MDA-MB-231 nude mice of human origin of Inhibition of transplanted tumors and intestinal flora under the influence of environmental estrogen bisphenol A.Human breast cancer cells MDA-MB-231 were inoculated subcutaneously into the right axillary of Balb/c-nu/nu female nude mice to establish a nude mouse xenograft model of human triple negative breast cancer,30 nude mice bearing triple-negative breast cancer were randomly divided into 5 groups,model group(distilled water every day),low、medium and high dose groups of bisphenol A and D-limonene(0.25 mL/kg,0.5 mL/kg,1 mL/kg),bisphenol A group(1 mL/kg),each group 6 mice;intragastric administration per day for 6 weeks.At the end of the experiment,the tumor mass and tumor volume of the tumor-bearing mice in the low,medium and high dose D-limonene group and the model group were observed and compared,and calculated the tumor inhibition rate,high-throughput sequencing technology was used to detect the distribution of intestinal flora in different groups of breast cancer tumor-bearing mice.Results:Tumors in the bisphenol A group increased more than the control tumor group,the volume and weight of breast cancer tumors in the low,medium and high dose bisphenol A and d-limonene group were smaller than those in the control group and the bisphenol A group;the species and abundance of intestinal flora increased after d-limonene treatment.The type and abundance of intestinal flora increased after d-limonene treatment,the abundance of verrucomicrobiota in medium and high dose d-limonene group was significantly higher than that in bisphenol a group and control group,the abundance of Bacteroidet was significantly lower than that of the BPA group and the control group.At the genus level,compared with the control group,the Bacteroides,Alloprevotella,Akkermansia,Lactobacillus,Helicobacter,and Parasutterella in the bisphenol A and d-limonene treatment groups were big different,but it did not reach significant significance.Conclusion:D-limonene has a certain inhibitory effect on breast cancer proliferation under the condition of bisphenol A,and it affects the number and abundance of the intestinal flora of nude mice with triple-negative breast cancer in the bisphenol A environment.