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乳腺癌细胞系暴露于不同比例的游离或共包封脂质体紫杉醇和阿霉素的短期和长期影响

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin.

作者信息

Franco Marina Santiago, Roque Marjorie Coimbra, Oliveira Mônica Cristina

机构信息

Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.

出版信息

Pharmaceutics. 2019 Apr 11;11(4):178. doi: 10.3390/pharmaceutics11040178.

DOI:10.3390/pharmaceutics11040178
PMID:30979090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6523953/
Abstract

BACKGROUND

Associating paclitaxel (PTX) to doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Protocols currently available consist in administering both drugs on their maximum tolerated dose, not taking into account the possible differences in efficacy due to their combination ratio. In the present study, the short and long-term cytotoxic effects as well as migratory effects of PTX, DXR, and its combinations at 10:1; 1:1 and 1:10 PTX:DXR molar ratios either free or co-encapsulated in liposomes were evaluated against three human BC cell lines (MDA-MB-231, MCF-7, and SKBR-3).

METHOD

The MTT assay was used to screen for synergy or antagonism between PTX and DXR and the combination index value was calculated using the CalcuSyn software. Nuclear morphological alterations were evaluated by staining the cells with Hoescht 33342. The investigation of senescence and clonogenicity of BC cell lines exposed to different treatments was also studied. In addition, the ability of these cells to migrate was assessed.

RESULTS

Taken together, the results presented herein allow us to suggest that there is no benefit in enhancing the PTX concentration above that of DXR in the combination for any of the three cell lines tested.

CONCLUSION

The developed liposomes co-encapsulating PTX and DXR in different molar ratios retained the biological properties of the mixture of free drugs and are valuable for planning new therapeutic strategies.

摘要

背景

将紫杉醇（PTX）与多柔比星（DXR）联合使用是乳腺癌（BC）治疗的主要化疗策略之一。目前可用的方案是两种药物都按最大耐受剂量给药，而没有考虑由于其联合比例不同可能导致的疗效差异。在本研究中，评估了游离的或共包封于脂质体中的PTX、DXR及其10:1、1:1和1:10 PTX:DXR摩尔比组合对三种人乳腺癌细胞系（MDA-MB-231、MCF-7和SKBR-3）的短期和长期细胞毒性作用以及迁移作用。

方法

采用MTT法筛选PTX和DXR之间的协同或拮抗作用，并使用CalcuSyn软件计算联合指数值。用Hoechst 33342对细胞进行染色，评估细胞核形态改变。还研究了暴露于不同处理下的乳腺癌细胞系衰老和克隆形成能力。此外，评估了这些细胞的迁移能力。

结果

综上所述，本文给出的结果使我们认为，对于所测试的三种细胞系中的任何一种，在联合用药中提高PTX浓度至高于DXR浓度并无益处。

结论

以不同摩尔比共包封PTX和DXR的脂质体保留了游离药物混合物的生物学特性，对规划新的治疗策略具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/82a31b86a2ee/pharmaceutics-11-00178-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/740c7363f588/pharmaceutics-11-00178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/70849ae6ae7e/pharmaceutics-11-00178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/d8566b60d1dd/pharmaceutics-11-00178-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/5adf574c7ec2/pharmaceutics-11-00178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/e952805a23eb/pharmaceutics-11-00178-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/82a31b86a2ee/pharmaceutics-11-00178-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/740c7363f588/pharmaceutics-11-00178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/70849ae6ae7e/pharmaceutics-11-00178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/d8566b60d1dd/pharmaceutics-11-00178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/addc82776742/pharmaceutics-11-00178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/5adf574c7ec2/pharmaceutics-11-00178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/e952805a23eb/pharmaceutics-11-00178-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a54b/6523953/82a31b86a2ee/pharmaceutics-11-00178-g007.jpg

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