Co-Culturing Cancer Cells and Normal Cells in a Biochip under Electrical Stimulation

Abstract

The ideal cancer therapeutic strategy is to inhibit the tumor with minimal influence on the normal tissue. Recently, applying an alternating electric field for inhibiting tumor was developed; but, it has not been adopted to be one of the regular therapeutic options. More basic scientific evidence is needed to clarify the efficacy and safety. In the current study, co-culturing cancer cells and normal cells under the electrical stimulation was conducted to provide evidence of this novel cancer therapy. A microfluidic cell culture biochip has been developed and consisted of nine culture chambers incorporating with stimulating electrodes. Cells cultured in the chamber received uniform electric field and cell viability was studied during the culture course. The electric field perturbs cell division and the correlation between cell proliferation rate and inhibition effect was studied among five cell lines, i.e., Huh7, HeLa, TW06, BM1, and HEL299. The results confirmed that cells with higher proliferation rate responded to a higher inhibition. In addition, co-culturing cancer cells and normal cells was conducted to mimic in vivo microenvironment that consists of both cancer and stromal cells. The cancer cells and normal cells were respectively transduced with green fluorescent protein and red fluorescent protein in order to differentiate the cells in a same culture chamber. During the culture course, the electric field was applied to the culture chamber and both cells simultaneously received the field. The results indicated that the growth of the cancer cells were inhibited while the normal cells were maintained. These results provided the evidence of the therapeutic efficacy and safety. Moreover, the microfluidic cell culture biochip could be used for the systematic and precise investigations of the cellular responses under the electrical stimulation.