牡荆苷对乳腺癌细胞转移瘤大鼠抗肿瘤作用及其对外周血Th22和IL-22的影响

Effect of vitexin on anti-tumor and peripheral blood Th22 and IL-22 in breast cancer cell metastases rats

目的探讨牡荆苷对乳腺癌细胞移植瘤抗肿瘤作用及对外周血辅助性T细胞22(Th22)和白细胞介素-22(IL-22)的影响。方法牡荆苷低、中、高剂量组及阳性对照组建立乳腺癌细胞移植瘤模型后,分别腹腔注射1、2、4 mg/mL的牡荆苷溶液及2.5 mg/mL的环磷酰胺,健康组和模型组腹腔注射等量生理盐水,连续14 d。检测各组外周血Th22和IL-22水平、肿瘤重量、抑瘤率及肿瘤组织中磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)mRNA和蛋白及磷酸化AKT(p-AKT)蛋白表达。结果牡荆苷低、中和高剂量组和阳性对照组肿瘤重量均低于模型组,且低剂量组>中剂量组>高剂量组和阳性对照组(P<0.05),抑瘤率低剂量组<中剂量组<高剂量组和阳性对照组(P<0.05),而牡荆苷高剂量组与阳性对照组上述指标差异无统计学意义(P>0.05)。牡荆苷低、中、高剂量组和阳性对照组外周血Th22、IL-22水平、癌组织PI3K、Bcl-2 mRNA和蛋白相对表达量及p-AKT/AKT均低于模型组,其中阳性对照组和低剂量组>中剂量组>高剂量组,但仍高于健康组(P<0.05);牡荆苷低、中、高剂量组和阳性对照组Bax mRNA和蛋白均高于模型组,其中阳性对照组和低剂量组<中剂量组<高剂量组,但仍低于健康组(P<0.05);牡荆苷低剂量组与阳性对照组上述指标差异无统计学意义(P>0.05)。结论牡荆苷具有明显抑制乳腺肿瘤作用,可能通过抑制PI3K/AKT信号通路,进而抑制Th22细胞及其效应因子IL-22分泌,发挥抗肿瘤作用。

Objective To investigate the anti-tumor effect of vitexin on breast cancer cell metastases rats and its effect on peripheral blood helper T cells 22(Th22)and interleukin-22(IL-22).Methods After the tumor models of breast cancer cell metastases were established,the low,medium and high dose groups and the positive control group were injected intraperitoneally with 1,2 and 4 mg/ml vitexin solution and 2.5 mg/mL cyclophosphamide.The healthy group and the model group were injected with the same amount of normal saline for 14 days.The levels of Th22 and IL-22 in peripheral blood,tumor mass,tumor inhibition rate and the expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),B lymphoma-2(Bcl-2),Bcl-2 related X protein(Bax)mRNA and protein,and phosphorylated AKT(p-AKT)protein in tumor tissues were detected.Results The tumor quatity of low,medium,high dose groups and positive control group were lower than that of the model group,and the sequence of whichwas low dose group>medium dose group>high dose group and positive control group(P<0.05),and there was no significant difference between the high dose group and positive control group(P>0.05).The levels of Th22 and IL-22 in the peripheral blood,the relative expressions of PI3K,Bcl-2 mRNA and protein and p-AKT/AKT in the cancer tissue of the low,medium,high dose of vitexin groups and positive control group were lower than those of the model group,and the sequence of whichwas positive control group and low dose group>medium dose group>high dose group,but those in the groups were still higher than inthe healthy group(P<0.05).The relative expressions of Bax mRNA and protein in the low,medium,high dose ofvitexin groups and positive control group were higher than those in the model group,and the sequence ofwhich was positive control group and low dose group<medium dose group<high dose group,but those in thegroups were still lower than in the healthy group(P<0.05);there was no statistical difference between the low dose ofvitexin group and positive control group(P>0.05).Conclusion Vitexin has a significant inhibitory effect on breast tumors,which may related to suppressing the secretion of Th22 cells and its effector IL-22 via inhibiting the PI3K/AKT signaling pathway.