An integrated microfluidic cell array for apoptosis and proliferation analysis induction of breast cancer cells.

In vitro sensitivity testing of tumor cells could rationalize and improve the choice of chemotherapy and hormone therapy. In this report, a microfluidic device made from poly(dimethylsiloxane) and glass was developed for an assay of drug induced cytotoxicity. We evaluated the apoptotic and proliferation-inhibitory effects of anticancer drugs mitomycin C (MMC) and tamoxifen (TAM) using MCF-7 breast cancer cells. MMC and TAM both induced apoptosis and inhibited proliferation of MCF-7 cells in a concentration-dependent manner. MMC caused the expression of antiapoptotic protein Bcl-2 a dose-dependent reduction in MCF-7 cells. The expression of Bcl-2 did not change significantly in MCF-7 cells treated by TAM. The results in the microfluidic device were correlated well with the data obtained from the parallel experiments carried out in the conventional culture plates. The developed microfluidic device could be a potential useful tool for high content screening and high throughput screening research.

[1]  P. Henson,et al.  Autoimmunity and apoptosis: refusing to go quietly , 2005, Nature Medicine.

[2]  P. Härkönen,et al.  Role of mitochondria in tamoxifen-induced rapid death of MCF-7 breast cancer cells , 2005, Apoptosis.

[3]  Andreas Makris,et al.  Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer , 2006, Breast Cancer Research.

[4]  Helene Andersson,et al.  Viability analysis and apoptosis induction of breast cancer cells in a microfluidic device: effect of cytostatic drugs , 2008, Biomedical microdevices.

[5]  M. Mojarrad,et al.  Autocrine human growth hormone expression leads to resistance of MCF-7 cells to tamoxifen , 2010, Medical oncology.

[6]  John Greenman,et al.  Development of a microfluidic device for the maintenance and interrogation of viable tissue biopsies. , 2008, Lab on a chip.

[7]  I. H. Engels,et al.  Apoptosis Resistance of MCF-7 Breast Carcinoma Cells to Ionizing Radiation Is Independent of p53 and Cell Cycle Control but Caused by the Lack of Caspase-3 and a Caffeine-Inhibitable Event , 2004, Cancer Research.

[8]  Jessica Melin,et al.  Microfluidic large-scale integration: the evolution of design rules for biological automation. , 2007, Annual review of biophysics and biomolecular structure.

[9]  Todd Thorsen,et al.  High-density microfluidic arrays for cell cytotoxicity analysis. , 2007, Lab on a chip.

[10]  Bingcheng Lin,et al.  Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device. , 2009, Lab on a chip.

[11]  Alexandrina Burlacu,et al.  Regulation of apoptosis by Bcl‐2 family proteins , 2003, Journal of cellular and molecular medicine.

[12]  Qingming Luo,et al.  Microfluidic chip: next-generation platform for systems biology. , 2009, Analytica chimica acta.

[13]  V. Ooi,et al.  Ethyl acetate extract of Patrinia scabiosaefolia downregulates anti-apoptotic Bcl-2/Bcl-X(L) expression, and induces apoptosis in human breast carcinoma MCF-7 cells independent of caspase-9 activation. , 2006, Journal of ethnopharmacology.

[14]  R. Hofheinz,et al.  Mitomycin C in the Treatment of Gastrointestinal Tumours: Recent Data and Perspectives , 2008, Oncology Research and Treatment.

[15]  B. Lin,et al.  Cell-based high content screening using an integrated microfluidic device. , 2007, Lab on a chip.

[16]  K. Tanabe,et al.  Targeted therapy against Bcl-2-related proteins in breast cancer cells , 2005, Breast Cancer Research.

[17]  J. Manson,et al.  Postmenopausal hormone therapy: an Endocrine Society scientific statement. , 2010, The Journal of clinical endocrinology and metabolism.

[18]  M. Borner,et al.  Mitomycin C induces apoptosis and caspase-8 and -9 processing through a caspase-3 and Fas-independent pathway , 2002, Cell Death and Differentiation.

[19]  H. Michna,et al.  The pure antiestrogen ICI 182780 is more effective in the induction of apoptosis and down regulation of BCL‐2 than tamoxifen in MCF‐7 cells , 1999, Breast Cancer Research and Treatment.

[20]  B. Katzenellenbogen,et al.  Estrogen receptors: selective ligands, partners, and distinctive pharmacology. , 2000, Recent progress in hormone research.

[21]  K. Maughan,et al.  Treatment of breast cancer. , 2010, American family physician.

[22]  R. Yu,et al.  Activation of caspase-3 and c-Jun NH2-terminal kinase-1 signaling pathways in tamoxifen-induced apoptosis of human breast cancer cells. , 2000, Cancer research.

[23]  G. Keating Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. , 2009, Drugs.

[24]  Raymond H. W. Lam,et al.  Building a better cell trap: Applying Lagrangian modeling to the design of microfluidic devices for cell biology , 2008 .

[25]  Donald Wlodkowic,et al.  Microfluidic single-cell array cytometry for the analysis of tumor apoptosis. , 2009, Analytical chemistry.

[26]  M. Arends,et al.  Tamoxifen increases apoptosis but does not influence markers of proliferation in an MCF-7 xenograft model of breast cancer. , 2000, Breast.

[27]  D. Chao,et al.  BCL-2 family: regulators of cell death. , 1998, Annual review of immunology.

[28]  Wei-Cheng Tian,et al.  Microfluidics for Biological Applications , 2008 .

[29]  Todd Thorsen,et al.  A self-contained microfluidic cell culture system , 2009, Biomedical microdevices.