甘草水提物联合Erastin对结直肠癌细胞在裸鼠体内铁死亡的影响

Effects of Gancao(Licorice)Extract Combined with Erastin on Iron Death of Colorectal Cancer Cells in Nude Mice

目的:探究甘草水提物(Licorice extract,LE)联合Erastin对结直肠癌(Colorectal cancer,CRC)细胞在裸鼠体内铁死亡的影响。方法:18只雌性BALB/c裸鼠皮下接种CACO2细胞建立CRC异种移植动物模型,随机分成模型组、LE组、LE+Erastin组,每组6只,给药4周。给药结束后,记录肿瘤体积和重量,HE染色观察肿瘤组织的病理变化,检测肿瘤细胞MDA和GSH含量,免疫组化检测肿瘤组织Ki-67和SLC7A11 mRNA表达,Western blot检测瘤组织SLC7A11、DPP4和NOX1蛋白的表达。结果:与模型组相比,LE组、LE+Erastin组小鼠肿瘤体积、质量显著降低(P<0.01);与LE组相比,LE+Erastin组小鼠肿瘤体积显著降低(P<0.01)。HE染色结果可见模型组小鼠肿瘤组织无明显改变;LE组小鼠肿瘤组织结构破坏,内有大量的淋巴细胞和白细胞浸润,出现大量坏死细胞;LE+Erastin组异型细胞减少,病理损伤程度更严重。与模型组相比,LE组、LE+Erastin组肿瘤组织MDA及DPP4蛋白含量显著升高(P<0.01),GSH含量降低,肿瘤组织SLC7A11、Ki-67表达及SLC7A11、NOX1蛋白水平显著降低(P<0.01);与LE组相比,LE+Erastin组肿瘤组织MDA含量水平显著升高,GSH含量降低,SLC7A11表达及SLC7A11、NOX1蛋白水平显著降低(P<0.05或P<0.01)。结论:LE联合Erastin能够促进CRC细胞在裸鼠体内发生铁死亡,进而抑制CRC细胞的生长。

Objective:To investigate the effects of Licorice extract(LE)combined with Erastin on iron death of colorectal cancer(CRC)cells in nude mice.Methods:18 SPF female BALB/C nude mice were ino-culated CACO2 cells to establish xenotransplantation animal model,and were randomly divided into model group,LE group and LE+Erastin group,6 in each group,administration for 4 weeks.After administration,the volume and weight of the tumor were recorded,the pathological damage of the tumor tissue was observed by HE staining,the content changes of MDA and GSH in the tumor cells were detected,and the expressions of Ki-67 and SLC7A11 in the tumor tissues were detected by immunohistochemistry.Western blot was used to detect SLC7A11,DPP4 and NOX1 protein expressions in tumor tissues.Results:Compared with model group,the vo-lume and mass of tumor in LE group and LE+Erastin group were significantly decreased(P<0.01),compared with LE group,the tumor volume LE+Erastin group was significantly decreased(P<0.01).HE staining results showed that no evident change in the tumor tissue of the model group mice;but the tumor tissue structure were destroyed and appeared a large number of lymphocytes,leukocytes and necrotic cells in LE group mice;and LE+Erastin group had fewer atypia cells and more severe pathological damage.Compared with model group,MDA and DPP4 protein contents in LE group and LE+Erastin group were significantly increased(P<0.01),GSH content,SLC7A11 and Ki-67expressions and SLC7A11 and NOX1 protein levels were significantly decreased(P<0.01);compared with LE group,MDA content of LE+Erastin group was significantly increased,GSH content,SLC7A11 expression,SLC7A11 and NOX1 protein levels were significantly decreased(P<0.05 or P<0.01).Conclusion:LE combined with Erastin can promote iron death and inhibit CRC cell growth in nude mice.