Electrical Stimulation Reverses Drug Resistance in Cancer Cells

NEW YORK MAR 21, 2006(Reuters Health) - Treatment of drug-resistant tumor cells with low intensity, low frequency AC electrical stimulation can improve the efficacy of chemotherapy by interfering with intrinsic drug extrusion mechanisms, new research shows.

The team had previously shown that such stimulation can reduce tumor cell proliferation through effects on potassium channels and can disrupt cytoskeletal mechanisms of cell division.

In the present study, Dr. Luca L. C. Cucullo and colleagues, from the Cleveland Clinic Lerner College of Medicine, tested the ability of electrical stimulation to improve the response to doxorubicin in several tumor cell lines overexpressing the multi-drug resistance gene, MDR1.

The experimental set-up, described in the April issue of BMC Cancer, involved well plates engineered to accommodate stainless steel electrodes connected to a waveform generator. Cells were exposed to short pulses of 50 Hz AC at 7.5 µA, with 10 seconds between pulses, for 3 days.

Treatment with the electricity did, in fact, make the tumor cells more sensitive to doxorubicin.  Further analysis showed that the stimulation achieved this effect by reducing MDR1 expression and by changing the distribution of the encoded protein from the plasma membrane to the cytoplasm.  Together, these changes allowed doxorubicin to gain entry into the cancer cell, rather than be actively extruded.

"These findings suggest a potential application of low intensity AC in the treatment of tumor growth by synergistically reducing neoplastic cell division and intrinsic tumor drug resistance," the authors state.

"In view of the widespread use of stimulators and stimulating electrodes for the treatment of a variety of other diseases, it seems possible that coupling electrical stimulation to current chemotherapy protocols will improve the efficacy of our therapeutic approach to neoplasms," they add.

SOURCE:

• BMC Cancer 2006.