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Anti-metastatic properties of a potent herbal combination in cell and mice models of triple negative breast cancer
Life Sciences ( IF 5.2 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.lfs.2019.117245 Laleh Arzi 1 , Reyhane Hoshyar 2 , Nazli Jafarzadeh 3 , Gholamhossein Riazi 1 , Majid Sadeghizadeh 3
Life Sciences ( IF 5.2 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.lfs.2019.117245 Laleh Arzi 1 , Reyhane Hoshyar 2 , Nazli Jafarzadeh 3 , Gholamhossein Riazi 1 , Majid Sadeghizadeh 3
Affiliation
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To determine the anti-metastatic potential of combinations of two bioactive carotenoids of saffron, crocin and crocetin, on 4T1 breast cancer and on a mice model of TNBC, and assess the effect of the most potent combination on the Wnt/β-catenin pathway. The effects of the carotenoid combinations on the viability of 4T1 cells were determined by MTT assay. The effects of the nontoxic doses on migration, mobility, invasion and adhesion to ECM were examined by scratch assay, Transwell/Matrigel-coated Transwell chamber and adhesion assay respectively. Tumors were inoculated by injecting mice with 4T1 cells. The weights and survival rates of the mice and tumor sizes were monitored. Histological analysis of the tissues was conducted. The expression levels of Wnt/β–catenin pathway genes were measured by Real-time PCR and western blotting. Treatment of 4T1 cells with combination doses inhibited viability in a dose-dependent manner. The nontoxic combinations significantly inhibited migration, cell mobility and invasion, also attenuating adhesion to ECM. The combination therapy mice possessed more weight, higher survival rates and smaller tumors. Histological examination detected remarkably fewer metastatic foci in their livers and lungs. It was also demonstrated that the combinations exerted anti-metastatic effects by disturbing the Wnt/β-catenin target genes in the liver and tumors. Our findings propose a carotenoid combination as an alternative potent herbal treatment for TNBC, which lacks the adverse effects associated with either chemotherapeutic agents or herb-chemotherapeutic drugs.
中文翻译：
有效草药组合在三阴性乳腺癌细胞和小鼠模型中的抗转移特性
确定藏红花、藏红花素和藏红花酸两种生物活性类胡萝卜素组合对 4T1 乳腺癌和 TNBC 小鼠模型的抗转移潜力，并评估最有效的组合对 Wnt/β-catenin 通路的影响。通过MTT测定确定类胡萝卜素组合对4T1细胞活力的影响。分别通过划痕实验、Transwell/Matrigel包被的Transwell小室和粘附实验检查无毒剂量对ECM迁移、移动、侵袭和粘附的影响。通过给小鼠注射4T1细胞来接种肿瘤。监测小鼠的体重和存活率以及肿瘤大小。对组织进行组织学分析。通过实时PCR和蛋白质印迹法测量Wnt/β-连环蛋白途径基因的表达水平。用组合剂量处理 4T1 细胞会以剂量依赖性方式抑制活力。无毒组合显着抑制迁移、细胞移动性和侵袭，还减弱了对 ECM 的粘附。联合治疗小鼠体重更大、存活率更高、肿瘤更小。组织学检查发现肝脏和肺部的转移灶明显减少。研究还表明，这些组合通过干扰肝脏和肿瘤中的 Wnt/β-catenin 靶基因发挥抗转移作用。我们的研究结果提出类胡萝卜素组合作为 TNBC 的替代有效草药治疗，它没有化疗药物或草药化疗药物相关的副作用。
更新日期：2020-01-08
中文翻译：
有效草药组合在三阴性乳腺癌细胞和小鼠模型中的抗转移特性
确定藏红花、藏红花素和藏红花酸两种生物活性类胡萝卜素组合对 4T1 乳腺癌和 TNBC 小鼠模型的抗转移潜力，并评估最有效的组合对 Wnt/β-catenin 通路的影响。通过MTT测定确定类胡萝卜素组合对4T1细胞活力的影响。分别通过划痕实验、Transwell/Matrigel包被的Transwell小室和粘附实验检查无毒剂量对ECM迁移、移动、侵袭和粘附的影响。通过给小鼠注射4T1细胞来接种肿瘤。监测小鼠的体重和存活率以及肿瘤大小。对组织进行组织学分析。通过实时PCR和蛋白质印迹法测量Wnt/β-连环蛋白途径基因的表达水平。用组合剂量处理 4T1 细胞会以剂量依赖性方式抑制活力。无毒组合显着抑制迁移、细胞移动性和侵袭，还减弱了对 ECM 的粘附。联合治疗小鼠体重更大、存活率更高、肿瘤更小。组织学检查发现肝脏和肺部的转移灶明显减少。研究还表明，这些组合通过干扰肝脏和肿瘤中的 Wnt/β-catenin 靶基因发挥抗转移作用。我们的研究结果提出类胡萝卜素组合作为 TNBC 的替代有效草药治疗，它没有化疗药物或草药化疗药物相关的副作用。
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