To overcome drug resistance in MDA-MB-231 breast cancer cells via paclitaxel loaded nanoemulsion

Introduction & objectives: Paclitaxel (PTX), is considered as one of the most effective chemotherapeutic compounds in the treatment of breast cancer. Nevertheless, one of the main problems regarding this reagent in is the developed drug resistance over time. Since a high percentage of PTX resistance in patients would be detectable at the time of initial diagnosis, it seems necessary to search for a new tactic to bypass the PTX resistance. In the current study, to overcome PTX resistance in breast cancer cells, we have established a new nanoemulsion system containing PTX.Materials & methods: A high-speed homogenization method was employed to fabricate PTX-nanoemulsion (PTX-NE) and for size evaluation DLS technique was used. Next, to examine cytotoxicity effects of PTX-NE on drug-resistant MDA-MB-231 cells, MTT assay was performed.Results: We have employed different concentrations of PTX (10nm, 50nm, 100nm, 200nm, 500nm) on the MDA-MB-231 breast cancer line for 24, 48 and 72 hours to assess their viability. Our results indicated that we could not achieve IC50 concentration even after 72 hours, which was indicative of drug resistance. To overcome this resistance, we have used a noneffective dose of TPGS, an inhibitor of MDR pump, combined with PTX. The data illustrated that combined with TPGS, 500nm concentration of PTX could kill almost 59% of the resistant cells. Moreover, data showed that IC50 concentration with PTX-NE was greatly decreased to 250nm, which was even less than the IC50 value in TPGS-PTX combination treatment.Conclusion: Nanoemulsion performed as a stable drug delivery system for paclitaxel which led to the reduction of PTX concentration. Hence, the severe PTX resistance in breast cancer could be effectively reduced by PTX-NE, which could deliver a potential strategy to treat multidrug resistance in this cancer.

کلیدواژه ها:

Drug resistance ، Breast cancer ، Paclitaxel