Observation of reversible, rapid adaptation to hypoxia in tumor cells cultured in a microfluidic device



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Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work, we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia with drug resistance to 2 μM staurosporine established within 30 minutes of hypoxia. We also observed rapid adaptation to normoxia within 30 minutes of exposure to laboratory air (20% oxygen). The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. In addition, we have developed a microfluidic device design, made entirely out of poly(dimethylsiloxane) (PDMS), which is capable of culturing cancers cells for over 96 hours to develop small tumor-like environments in a low shear, observable culture environment. The results of this work will help create a method of culturing tumor forming cancer cells in an environment that is more comparable to the natural surroundings of a tumor.



Cell culture, Microfluidics, Cancer