Avid Khamenehfar Paul CH Li and Elaine LH Leung
Keywords: Targeted drugs, lung cancer cells, multidrug resistance, fluorescent measurement, same single cell control.
Abstract: For high selectivity in cancer therapy, molecular-targeted drugs such as gefitinib are used. But there is drug resistance to its use on non-small cell lung cancer (NSCLC). In this case, chemotherapeutic drugs such as paclitaxel (PTX) will be used. However, multidrug resistance (MDR) occurs when the cancer cells resist chemotherapeutic drugs by pumping them out of the cells. MDR inhibitors such as cyclosporine A (CsA) can block MDR protein action and thus enhance the drug uptake in the cancer cells. This enhancement is clearly observed in real-time by conducting the same single cell analysis (SASCA) using a microfluidic biochip. The NSCLC cells such as NCI-H1650 were used for the study. By the SASCA method, the NCI-H1650 cell was found to have low initial PTX accumulation, and the treatment of the same lung cancer cell with PTX in the presence of CsA notably enhanced drug accumulation, indicating CsA is a MDR inhibitor. Moreover, gefitinib is found to be a MDR inhibitor and it enhances the drug accumulation in NCI-H1650 cells too. Therefore, we hypothesize when both paclitaxel and gefitinib are used in combination, NSCLC cells can be killed, whether they are gefitinib-resistant or multidrug resistant or not.
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