易普利姆玛对Lewis肺癌小鼠体内PTHrP表达的影响及与癌细胞衰老的关系

Effect of Lpilimumab on the Expression of PTHr P in Lewis Lung Cancer Mice and Its Relationship with the Aging of Cancer Cells

目的建立Lewis肺癌小鼠模型,观察Ipilimumab对荷瘤小鼠体内PTHr P及MCT1表达的影响并探讨与癌细胞衰老的关系。方法取C57BL/6小鼠共30只,建立Lewis肺癌小鼠模型,随机分为对照组、低剂量处理组、高剂量处理组,每组10只。开始给药,给药剂量与方法:低浓度Ipilimumab处理组3 mg/kg,高浓度Ipilimumab处理组5 mg/kg,共给药5次,对照组给予等量生理盐水。采用免疫组织化学法检测3组中PTHr P、MCT1的表达。结果 3组动物细胞PTHr P蛋白的分泌及MCT1的阳性表达率高度一致,且随Ipilimumab浓度的增高而增高,第3组表达水平较第2组和第1组明显升高,有统计学意义(P<0.05),第2组表达水平较第1组明显升高,有统计学意义(P<0.05)。且2个指标阳性表达率均与细胞衰老相关基因βGal的表达呈显著负相关性(P<0.05)。结论 Ipilimumab处理后的荷瘤小鼠通过上调PTHr P、MCT1的表达,延缓癌细胞的衰老,最终引起癌细胞侵袭或转移。

Objective To establish Lewis lung cancer mice model, and observe the effect of ipilimumab on PTHrP and MCT1 in tumor bearing mice and its relationship with cancer cell senescence. Methods A total of 30 Lewis mice which was es- tablished Lewis lung cancer mice model were divided into the control group, low dose treatment group and high dose treatment group, and each group with 10 cases. Start to give medicine, dosage and methods：low concentration ipilimumab treatment group 3mg/kg, high concentration ipilimumab treatment group 5mg/kg, a total of 5 times, the control group to give the same amount of normal saline. The expression of PTHrP and MCT1 in the 3 groups was detected by immunohistochemistry. Results The positive expression of PTHrP protein secretion and MCT1 in the 3 groups of animal cells rate highly consistent and tend to increase with the increasing of the concentration of ipilimumab,2 indicators in expression in group 3 than in group 2 and group 1 expression increased significantly, there had statistical difference （ P 〈 0.05 ） ;in group 2 expression than in the group 1 expression was signifi- cantly increased, there had statistical difference （ P 〈 0.05 ）. And the positive expression rate of the 2 indicators were significantly negative correlated with the expression of cell senescence associated gene Gal, and the results were statistically significant （P 〈 0.05 ）. Conclusion Ipilimumab treatment of tumor bearing mice by up regulation of MCT1, PTHrP expression, delay the aging of cancer cells,and eventually cause cancer cell invasion or metastasis.