טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentPardoviz-Kedmi Ella
SubjectThe Effect of the Anesthetic Drug Propofol on the
Accumulation of Chemotherapy Drugs in Cell Lines
DepartmentDepartment of Biology
Supervisor Professor Gera Eytan


Abstract

Chemotherapy is currently the main treatment for most common cancer cases. Resistance to multiple drugs referred to as multidrug resistance (MDR) is a major impediment to the successful treatment of various human cancers. One of the MDR mechanisms in tumor cells is due to overexpression of energy dependent efflux pumps, known as multidrug transporters or “ MDR proteins”. The two best described transporters mediating MDR are P-glycoprotein (Pgp) and the Multidrug Resistance Protein (MRP1).

Propofol (2,6 diisopropylphenol) is an intravenous anesthetic that is being used for induction and maintenance of general anesthesia. Propofol has the ability to fluidize membranes. In this study we examined for the first time the capacity of propofol to modulate the MDR phenomenon.

The main goal of this research was to find out if propofol acts like a modulator and to explore its modulation mechanism. Propofol modulated the MDR phenomenon in both animal and human cell-lines.

We found that propofol accelerates the flip-flop of drugs across membranes and influx rate of drugs into cells and also inhibits the ATPase activity of the Pgp.

Direct measurement of dye efflux from cells showed surprisingly that propofol accelerates the active efflux rate.

We suggest that the main effect of propofol, which causes the modulation effect, is the increase in the influx rate of drugs through the membrane.

It can be expected that application of general anesthetics such propofol which is an efficient membrane fluidizer in combination with a chemotherapeutic regimen containing MDR-type drugs could achieve reversal of MDR.