乳铁蛋白六肽降低人卵巢癌细胞的耐药性及其机制  

Lactoferrin hexapeptide reduces the drug resistance of human ovarian cancer cells and its mechanism

作　　者：刘会 郭若文 徐恰 刘力伟 刘芸 秦宜德[1] Liu Hui;Guo Ruowen;Xu Qia(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》2021年第10期1595-1601,1611,共8页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81472448)。

摘　　要：目的研究乳铁蛋白六肽(LfcinB4-9)降低人卵巢癌细胞的耐药性并探究其作用可能的机制。方法MTT检测顺铂(DDP)联合LfcinB4-9对人卵巢癌细胞SKOV3、SKOV3/DDP、CI3K、CI3K/DDP的增殖抑制;HE细胞染色切片实验检测人卵巢细胞经加药处理后细胞形态发生的变化;平板克隆实验检测DDP联合LfcinB4-9对人卵巢癌细胞克隆形成能力的影响;Transwell实验检测DDP联合LfcinB4-9对人卵巢癌细胞侵袭能力的影响;qRT-PCR检测人卵巢癌细胞在LfcinB4-9和DDP联合处理下HSF1、HSP70、OPTN等基因的表达情况。结果LfcinB4-9和DDP联合作用对卵巢癌细胞的抑制率明显高于DDP单独作用组(P<0.05或P<0.01),人卵巢细胞经DDP联合LfcinB4-9作用后细胞形态变化显著大于DDP单独作用组,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和侵袭能力均显著降低(P<0.05或P<0.01)。qRT-PCR实验显示,DDP联合LfcinB4-9时HSF1、HSP70、OPTN等耐药相关基因表达显著低于对照组和DDP单独组。结论LfcinB4-9与DDP联合作用后明显增强了卵巢癌细胞对DDP的敏感性,其作用是通过降低HSF1、HSP70、OPTN等基因表达,通过HSF1-HSP70-耐药蛋白的信号途径来实现的。Objective To study lactoferrin hexapeptide(LfcinB 4-9)to reduce the drug resistance of human ovarian cancer cells and explore its possible mechanism of action.Methods MTT was used to detect the proliferation inhibition of cis-dichlorodiammine platinum(DDP)combined with LfcinB4-9 in human ovarian cancer cells SKOV3,SKOV3/DDP,CI3K,CI3K/DDP.The morphologic changes of human ovarian cells were detected by HE staining and section assay.The effect of DDP combined with LfcinB4-9 on the clone formation ability of human ovarian cancer cells was detected by plate cloning assay;Transwell assay was used to detect the effect of DDP combined with LfcinB4-9 on the invasion ability of human ovarian cancer cells.qRT-PCR was used to detect the expression of HSF1,HSP70,OPTN and other genes in human ovarian cancer cells treated with LfcinB4-9 and DDP.Results The results showed that the combined effect of LfcinB4-9 and DDP had a significantly higher inhibitory rate on ovarian cancer cells that of DDP alone(P<0.05 or P<0.01).The cell morphology of human ovarian cells was significantly changed after DDP combined with LfcinB4-9.Compared with DDP alone group,the clone formation ability and invasion ability of human ovarian cancer cells were significantly reduced by DDP combined with LfcinB4-9(P<0.05 or P<0.01).The qRT-PCR assay showed that the expressions of HSF1,HSP70,OPTN and other drug-resistant related genes in DDP combined with LfcinB4-9 were significantly lower than those in the control group and DDP alone group.Conclusion The combined effect of LfcinB4-9 and DDP significantly enhances the sensitivity of ovarian cancer cells to DDP.Its effect is achieved by reducing the expression of HSF1,HSP70,OPTN and other genes through the signalling pathway of HSF1-HSP70-resistant protein.

关 键 词：卵巢癌细胞 乳铁蛋白六肽 顺铂 耐药性 基因表达 

分 类 号：R737.31[医药卫生—肿瘤]