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Viability analysis and apoptosis induction of breast cancer cells in a microfluidic device: effect of cytostatic drugs

机译:微流控设备中乳腺癌细胞的活力分析和凋亡诱导:细胞抑制药物的作用

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摘要

Breast cancer is the leading cause of cancer deaths among non-smoking women worldwide. At the moment the treatment regime is such that patients receive different chemotherapeutic and/or hormonal treatments dependent on the hormone receptor status, the menopausal status and age. However, in vitro sensitivity testing of tumor biopsies could rationalize and improve the choice of chemo- and hormone therapy. Lab-on-a-Chip devices, using microfluidic techniques, make detailed cellular analysis possible using fewer cells, enabling working with a patients’ own cells and performing chemo- and hormone sensitivity testing in an ex vivo setting. This article describes the development of two microfluidic devices made in poly(dimethylsiloxane) (PDMS) to validate the cell culture properties and analyze the chemosensitivity of MCF-7 cells (estrogen receptor positive human breast cancer cells) in response to the drug staurosporine (SSP). In both cases, cell viability was assessed using the life-stain Calcein-AM (CAAM) and the death dye propidium iodide (PI). MCF-7 cells could be statically cultured for up to 7 days in the microfluidic chip. A 30 min flow with SSP and a subsequent 24 h static incubation in the incubator induced apoptosis in MCF-7 cells, as shown by a disappearance of the aggregate-like morphology, a decrease in CAAM staining and an increase in PI staining. This work provides valuable leads to develop a microfluidic chip to test the chemosensitivity of tumor cells in response to therapeutics and in this way improve cancer treatment towards personalized medicine.
机译:乳腺癌是全世界非吸烟女性中癌症死亡的主要原因。目前的治疗方案是使患者根据激素受体状态,更年期状态和年龄接受不同的化学治疗和/或激素治疗。但是,肿瘤活检的体外敏感性测试可以合理化和改善化学疗法和激素疗法的选择。芯片实验室设备使用微流技术,可使用更少的细胞进行详细的细胞分析,从而能够与患者自己的细胞一起工作,并在离体设置下进行化学和激素敏感性测试。本文介绍了两种由聚二甲基硅氧烷(PDMS)制造的微流体装置的开发,以验证其细胞培养特性并分析MCF-7细胞(雌激素受体阳性的人类乳腺癌细胞)对药物星形孢菌素(SSP)的化学敏感性)。在这两种情况下,均使用生命染色钙黄绿素-AM(CAAM)和死亡染料碘化丙锭(PI)评估细胞活力。 MCF-7细胞可以在微流控芯片中静态培养长达7天。用SSP流动30分钟,然后在培养箱中进行24小时静态培养,可诱导MCF-7细胞凋亡,如聚集体形态消失,CAAM染色减少和PI染色增加所显示。这项工作为开发微流控芯片以测试肿瘤细胞对治疗剂的化学敏感性提供了有价值的线索,并以此方式改善了针对个性化药物的癌症治疗。

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