P-glycoprotein-mediated multidrug resistance is modulated by pretreatment with chemosensitizers in HCT-8 carcinoma cells in vitro.
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- Published online on: May 1, 1998 https://doi.org/10.3892/ijo.12.5.1137
- Pages: 1137-1179
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Abstract
The effects of pretreatment with the multidrug resistance (MDR) modulators verapamil (VPM), tamoxifen (TMX), cyclosporin A (CsA), and SDZ PSC833 (PSC) on drug sensitivity of the P-glycoprotein (Pgp) expressing human ileocecal carcinoma cell line HCT-8 is described. Following pretreatment of 2, 16 and 48 h with the individual modulators, rhodamine 123 efflux (RHO), transepithelial vinblastine transport (VIN) across treated HCT-8 monolayers, and chemosensitivity to doxorubicin (DOX) were determined and compared to Pgp protein expression and phosphorylation. After 2 h, VPM, TMX, CsA and PSC inhibited RHO efflux and VIN transport and increased the chemosensitivity of HCT-8 to DOX significantly. Prolonged exposure failed to further increase inhibition of Pgp-mediated transport, but in contrast maximized phosphorylation of Pgp (16 h) and Pgp protein expression (48 h), respectively.
