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Cancer Res. 2010 Oct 1;70(19):7723-33. doi: 10.1158/0008-5472.CAN-09-4360. Epub 2010 Sep 14.

Image-based chemical screening identifies drug efflux inhibitors in lung cancer cells.

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  • 1Medical Systems Biology Laboratory, Center for Bioengineering and Informatics, The Methodist Hospital Research Institute, Houston, Texas 77030, USA.


Cancer cells with active drug efflux capability are multidrug resistant and pose a significant obstacle for the efficacy of chemotherapy. Moreover, recent evidence suggests that high drug efflux cancer cells (HDECC) may be selectively enriched with stem-like cancer cells, which are believed to be the cause for tumor initiation and recurrence. There is a great need for therapeutic reagents that are capable of eliminating HDECCs. We developed an image-based high-content screening (HCS) system to specifically identify and analyze the HDECC population in lung cancer cells. Using the system, we screened 1,280 pharmacologically active compounds that identified 12 potent HDECC inhibitors. It is shown that these inhibitors are able to overcome multidrug resistance (MDR) and sensitize HDECCs to chemotherapeutic drugs, or directly reduce the tumorigenicity of lung cancer cells possibly by affecting stem-like cancer cells. The HCS system we established provides a new approach for identifying therapeutic reagents overcoming MDR. The compounds identified by the screening may potentially be used as potential adjuvant to improve the efficacy of chemotherapeutic drugs.

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