Viability analysis and apoptosis induction of breast cancer cells in a microfluidic device: effect of cytostatic drugs.
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.
Komen
Job
J
BIOS, the Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500 AE, Enschede, The Netherlands.
Wolbers
Floor
F
Franke
Henk R
HR
Andersson
Helene
H
Vermes
Istvan
I
van den Berg
Albert
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001681:Biological Assay / Q000295:instrumentation* / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D011108:Polymers / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors
D000970:Antineoplastic Agents; D004129:Dimethylpolysiloxanes; D005452:Fluoresceins; D005456:Fluorescent Dyes; D011108:Polymers; C085925:calcein AM; C013830:baysilon; D019311:Staurosporine