Lapatinib enhances paclitaxel toxicity in MCF-7, T47D, and MDA-MB-321 breast cancer cells
Alicja Zajdel, Joanna Nycz, Adam Wilczok
Abstract
Paclitaxel (PTX) is used to treat breast cancer both as a monotherapy and in combination with other anticancer drugs. Chemoresistance is one of the main reasons for the failure of breast cancer treatment. Mechanisms which contribute to multidrug resistance of breast cancer cells to PTX include the active removal of the drug from the cell related to the increased activity of ABC family membrane transporters. Lapatinib (LAP) has been approved by the FDA in combination with other anticancer agents for the treatment of HER2-positive breast cancer. LAP can reverse chemoresistance by interaction with ABC transporters. Therefore the aim of the study was to investigate whether LAP is able to potentiate PTX toxicity in MCF-7, T47D, and MDA-MB-321 breast cancer cells which do not express the HER-2. It was found that LAP inhibited the PTX efflux, increased its intracellular concentration and thus significantly increased the anticancer activity of PTX. The combination of PTX and LAP can be useful in HER2-negative breast cancer treatment.