Date of Degree
Master of Science (MS)
The purpose of this study was to investigate the development of chemotherapeutic resistance to paclitaxel in ovarian cancer cells after treatment with drugs that are substrates for P-glycoprotein (PGP). A core concept of this experiment was to identify if PGP substrate drugs could also act as PGP inducers after prolonged treatment in SKOV-3 ovarian cancer cells. In order to test this, SKOV-3 cells were exposed to either fexofenadine, a PGP substrate used as an antihistamine, or the chemotherapeutic drug vinblastine. After 42 days of drug treatment, ABCB1 gene expression was measured by qRT-PCR. Analysis of ABCB1 expression in treated cells revealed that fexofenadine was unable to significantly induce gene expression in SKOV-3 cells. Although some cells treated with vinblastine did exhibit some significant increases in ABCB1 expression, vinblastine exposure overall could not reliably induce ABCB1 gene expression within SKOV-3 cells. After testing for PGP induction, treated cells were exposed paclitaxel and tested for cell survivability. The results indicated that cells with induced PGP exhibited reduced survivability against paclitaxel exposure.
Penn, Ryker, "Investigation of P-Glycoprotein (PGP) Induction by PGP Substrates to Induce Paclitaxel Resistance in Ovarian Cancer Cells" (2018). Theses & Dissertations. 366.