乳铁蛋白活性六肽(LfcinB 4-9)增加人宫颈癌细胞对顺铂的敏感性及其机制  

Lactoferrin active hexapeptide(LfcinB 4-9)increases the sensitivity of human cervical cancer cells to cisplatin and its mechanism

作　　者：刘芸 徐恰 刘力伟 戚楠[1] 秦宜德[1,2] Liu Yun;Xu Qia;Liu Liwei;Qi Nan;Qin Yide(Dept of Biochemistry and Molecular Biology,School of Basic Medicine,Anhui Medical University,Hefei 230032;Dept of Immunology,School of Basic Medicine,Anhui Medical University,Hefei 230032)

机构地区：[1]安徽医科大学基础医学院生物化学与分子生物学教研室,合肥230032 [2]安徽医科大学基础医学院免疫教研室,合肥230032

出　　处：《安徽医科大学学报》2022年第8期1268-1274,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81472448)。

摘　　要：目的研究乳铁蛋白活性六肽(LfcinB 4-9)增加人宫颈癌细胞对顺铂的敏感性并探究其作用机制。方法MTT检测顺铂(DDP)联合不同浓度的LfcinB 4-9对人宫颈癌细胞Hela细胞株、敲除p62基因的Hela细胞株(Hela/KO p62)增殖的影响;平板克隆实验检测DDP联合LfcinB 4-9对人宫颈癌细胞克隆形成能力的影响;流式细胞术实验检测联合用药对人宫颈癌细胞凋亡的影响;qRT-PCR检测联合用药对人宫颈癌细胞Hela、Hela/KO p62中SIAH、PSMA、β-catenin等基因表达水平的影响;Western blot检测联合用药对人宫颈癌细胞中SIAH、PSMA、β-catenin等蛋白表达水平的影响。结果LfcinB 4-9和DDP联合用药对宫颈癌细胞的抑制率高于DDP单独作用组或单独LfcinB 4-9组(P<0.05或P<0.01),与DDP单独组相比,DDP联合LfcinB4-9作用后人卵巢癌细胞克隆形成能力降低,凋亡增加(P<0.05或P<0.01)。qRT-PCR和Western blot实验显示,DDP联合LfcinB 4-9作用时联合用药SIAH、PSMA1的表达量增加,而β-catenin的表达量降低。结论LfcinB4-9与DDP联合作用后增强了宫颈癌细胞对DDP的敏感性,其作用是通过蛋白酶体途径来实现的。Objective To study the sensitivity of human cervical cancer cells to cisplatin which increased by the lactoferrin active hexapeptide(LfcinB 4-9)and to investigate its mechanism.Methods MTT was used to detect the proliferation inhibition of cisplatin(DDP)combined with different concentrations of LfcinB 4-9 on human cervical cancer Hela cell line and the Hela cell line with the p62 gene knocked out(Hela/KO p62).The plate cloning assay was performed to detect the effect of DDP combined with LfcinB 4-9 on the cloning ability of human cervical cancer cells.The effect of DDP combined with LfcinB 4-9 on the apoptosis of human cervical cancer cells was detected by flow cytometry.RT-qPCR and Western blot were used to detect the expression levels of genes and protein such as SIAH,PSMA,andβ-catenin in cancer cells Hela and Hela/KO p62.Results The inhibitory rate of the combination of LfcinB 4-9 and DDP on cervical cancer cells was significantly higher than that of DDP alone or LfcinB 4-9 alone(P<0.05 or P<0.01).Compared with DDP group,the cloning ability of human ovarian cancer cells was significantly reduced,and apoptosis increased in combined treatment(P<0.05 or P<0.01).The qRT-PCR and Western blot assay showed that when DDP combined with LfcinB 4-9,the expression of SIAH and PSMA1 increased,while the expression ofβ-catenin decreased.Conclusion The combined effect of LfcinB4-9 and DDP significantly enhances the sensitivity of cervical cancer cells to DDP,which is achieved via the proteasome pathway.

关 键 词：宫颈癌细胞 乳源六肽 顺铂 耐药性 基因表达 

分 类 号：R737.33[医药卫生—肿瘤]