整合素αvβ3抑制剂Cyclo-RGDfK对纤连蛋白诱导乳腺上皮细胞间质转化的影响

目的本研究探讨整合素αvβ3抑制剂(Cyclo-RGDfK)对纤连蛋白(fibronectin,FN)诱导人乳腺上皮细胞MCF-10A上皮间质转化的影响。方法体外传代培养MCF-10A细胞,采用FN诱导建立上皮间质转化(EMT)模型。Western blot实验检测αv integrin、β3 integrin、上皮标志物E-cadherin和间充质标志物N-cadherin、Vimentin的蛋白表达;划痕修复实验和Transwell小室实验检测细胞的迁移和侵袭能力。结果 Western blot结果显示FN作用48 h后可明显增强αv integrin、β3 integrin、N-cadherin、Vimentin的蛋白表达,下调E-cadherin蛋白表达,在给予Cyclo-RGDfK作用后,FN诱导的N-cadherin和Vimentin表达上调和E-cadherin表达下调被明显逆转;划痕修复实验和Transwell小室实验结果表明,FN能显著增强MCF-10A细胞迁移和侵袭能力,Cyclo-RGDfK能显著抑制FN的诱导作用。结论 Cyclo-RGDfK能抑制FN诱导乳腺上皮细胞MCF-10A的EMT过程,降低细胞的侵袭和迁移能力,其可能是治疗乳腺癌转移的潜在药物。     

自我效能增强干预对膝关节骨折术后患者功能锻炼康复效果的影响

自我效能这一概念的提出是在20世纪70年代,由美国著名行为主义心理学家班杜拉在其社会认知理论中提出的一核心概念,其定义为"个体对自身能否完成某一活动所具有的能力判断和信念"或"个体在某一活动任务时的胜任感,及其自信、自珍、自尊等方面的感受",概括起来讲,所谓自我效能感就是"指人们对自身完成某项任务或工作行为能力的信念"[1].这一概念得到了教育学、心理学等学术界的关注,自我效能理论为行为改变提供了理论框架.现将这一理论引用到膝关节骨折术后患者的康复功能锻炼中,观察研究增强自我效能干预对膝关节骨折术后患者功能锻炼康复效果的影响.     

HIF-1α调控4-羟基他莫昔芬对乳腺癌MCF-7细胞敏感性的研究

目的 该研究通过建立人乳腺癌4-羟基他莫昔芬(4-OHT)耐药细胞系(MCF-7/TR),探究低氧诱导因子1α(HIF-1α)对乳腺癌MCF-7细胞4-OHT耐药的影响。方法 采用他莫昔芬的体内活性形式4-OHT建立乳腺癌耐药细胞MCF-7/TR。MTT实验检测4-OHT对乳腺癌细胞MCF-7、MCF-7/TR细胞活力的影响,并测定耐药指数(RI);Western blot检测MCF-7、MCF-7/TR细胞中HIF-1α蛋白的表达水平;采用MTT法和流式细胞术AV/PI双染法检测,HIF-1α抑制剂(LW6)或siRNA HIF-1α干预作用后4-OHT对MCF-7/TR细胞的影响以及HIF-1α稳定剂（FG-4592）处理后4-OHT对MCF-7细胞的影响。结果 结果显示,MCF-7/TR耐药细胞株成功构建,其RI为(5.56±0.80);与MCF-7细胞相比,MCF-7/TR细胞中HIF-1α高表达,且4-OHT作用后MCF-7/TR细胞中HIF-1α的表达水平上调;给予LW6或沉默HIF-1α的表达后,HIF-1α的表达下调增强了4-OHT对MCF-7/TR细胞的抑制作用;给予...     

GPER inhibitor increases tamoxifen-induced apoptosis in T-47DTR-resistant cells北大核心CSCD

Aim To study the effect of G protein-coupled estrogen receptor(GPER)inhibitor G15 on the sensitivity of breast cancer tamoxifen-resistant cells to T-47DTR. Methods Experiments were carried out with 4-hydroxytamoxifen(4-OHT),the active form of tamoxifen in vivo. The sensitivity of tamoxifen-resistant breast cancer cell line T-47DTR and its parental cell line T-47D to tamoxifen was detected by MTT assay; the expression of GPER protein was analyzed by plasma separation of inhibitor G15; the effect of 4-OHT combined with G15 on the apoptosis of T-47DTR cells was analyzed by flow cytometry AnnexinV-FITC/PI double staining; the expression levels of apoptosis-related proteins Bax,Bcl-2,caspase-3,cleaved caspase-3,caspase-9,cleaved caspase-9 were analysed by Western blot. Results(1)Compared with the parental cell T-47D,the resistance of T-47DTR-resistant cells to 4-OHT was significantly enhanced.(2)When 4-OHT(2 μmol·L-1)was administered,the membrane distribution of GPER increased,indicating that GPER was activated in T-47DTR-resistant cells compared with the control group; Compared with OHT,the use of G15(5 μmol·L-1)and OHT significantly reduced the expression of GPER.(3)GPER inhibitor G15 could increase the apoptotic rate of T-47DTR-resistant cells while down-regulating the anti-apoptotic protein Bcl-2 and up-regulating the expression of pro-apoptotic proteins Bax,cleaved caspase-3,cleaved caspase-9. Conclusions The GPER inhibitor G15 increases the apoptosis of T-47DTR cells and restores the sensitivity of drug-resistant cells to tamoxifen. © 2023 Publication Centre of Anhui Medical University. All rights reserved.