三阴性乳腺癌中紫杉醇和达沙替尼的体外和体内研究效果
In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study.
发表日期:2023 Aug
作者:
Ioannis D Passos, Dimochristos Papadimitriou, Areti Katsouda, Georgios E Papavasileiou, Apostolos Galatas, Panagiotis Tzitzis, Alexandra Mpakosi, Maria Mironidou-Tzouveleki
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
引言 三阴乳腺癌(TNBC)是一组异质性肿瘤,其共同特点是具有明显的侵略性,并且与其他亚型的乳腺癌相比,在转移性情况下复发率更高,总体生存率更低。迄今为止,尚未批准一种针对TNBC治疗的靶向疗法,细胞毒性化疗仍然是标准治疗方法。在本实验研究中,我们对TNBC细胞系(体外)和TNBC肿瘤异种移植小鼠模型(体内)进行了化疗药物多西他赛和bcr/abl激酶抑制剂达沙替尼的影响研究。 材料与方法 培养并用多西他赛和达沙替尼(5 nM至100 nM)不同浓度处理TNBC细胞系。通过流式细胞术研究细胞死亡和凋亡。然后,在BALB/c裸小鼠体内注射TNBC细胞系以形成肿瘤。创建四组小鼠(A组:对照组;B组:DOC组;C组:DAS组;D组:DOC + DAS组),分别给予药物及其组合治疗。获取肿瘤,以10%福尔马林固定,包埋在石蜡中,并发送进行进一步的组织学评估(苏木精-伊红染色和免疫组织化学分析)以评估抑制肿瘤生长的效果。 结果 多西他赛的细胞毒性效应在统计学上显著,对凋亡的影响较小。达沙替尼在体外和体内的作用在统计学上显著,从凋亡和肿瘤缩小方面效果显著,副作用较小。 结论 TNBC是一种难以治疗的肿瘤疾病,即使在实验环境中也是如此。关于将靶向疗法(达沙替尼)与传统的细胞毒性疗法(多西他赛)联合使用的有希望的结果已经显示出来,但还需进一步评估。版权所有 © 2023,Passos等人。
Introduction Triple-negative breast cancer (TNBC) comprises a heterogeneous group of tumors with a single trait in common: an evident aggressive nature with higher rates of relapse and lower overall survival in the metastatic context when compared to other subtypes of breast cancer. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In the present experimental study, we examine the effects of the chemotherapeutic docetaxel and the bcr/abl kinase inhibitor dasatinib on TNBC cell lines (in vitro) and on TNBC tumor xenograft mouse models (in vivo). Materials and methods TNBC cell lines were cultivated and treated with various concentrations of docetaxel and dasatinib (5 nM to 100 nM). Cell death and apoptosis were studied by flow cytometry. TNBC cell lines were then injected in BALB/c athymic nude mice to express the tumor in vivo. Four groups of mice were created (group A: control; group B: DOC; group C: DAS; group D: DOC + DAS) and treated, respectively, with the drugs and their combination. Tumors were obtained, maintained in a 10% formaldehyde solution, embedded in paraffin, and sent for further histological evaluation (hematoxylin-eosin staining and immune-histochemical analysis) to assess the tumor growth inhibition. Results The cytotoxic effects of docetaxel seem statistically important, with little effect on apoptosis. The effect of dasatinib in vitro and vivo is statistically important, in terms of apoptosis and tumor reduction, with little adverse effects. Conclusions TNBC is a difficult-to-treat oncologic condition, even in an experimental setting. Promising results concerning the addition of targeted therapies (dasatinib) to the conventional cytotoxic ones (docetaxel) have been shown, awaiting further evaluation.Copyright © 2023, Passos et al.