Impact of BCRP/MXR, MRP1 and MDR1/P‐Glycoprotein on thermoresistant variants of atypical and classical multidrug resistant cancer cells

Abstract

The impact of the ABC transporters breast cancer resistance protein/mitoxantrone resistance associated transporter (BCRP/MXR), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance gene-1/Pglycoprotein (MDR1/PGP) on the multidrug resistance (MDR) phenotype in chemoresistance and thermoresistance was investigated in the parental human gastric carcinoma cell line EPG85-257P, the atypical MDR subline EPG85- 257RNOV, the classical MDR subline EPG85-257RDB and their thermoresistant counterparts EPG85-257P-TR, EPG85-257RNOV-TR and EPG85-257RDB-TR. Within the atypical MDR subline EPG85-257RNOV expression of BCRP/MXR and of MRP1 were clearly enhanced (vs. parental and classical MDR lines). MDR1/PGP expression was distinctly elevated in the classical MDR subline EPG85-257RDB (vs. parental and atypical MDR sublines). In all thermoresistant counterparts basal expression of BCRP/MXR, MRP1 and MDR1/PGPwas increased relative to thermosensitive sublines. Although it could be shown that the overexpressed ABC transporters were functionally active, however, no decreased drug accumulations of doxorubicin, mitoxantrone and rhodamine 123 were observed. Thus, expression of BCRP/MXR, MRP1 and MDR1/PGP was found to be dependent on the appropriate type of chemoresistance; correlating with a classical or atypical MDR phenotype. Within the thermoresistant variants, however, the increase in ABC transporter expression did obviously not influence the MDR phenotype.

A novel indole ethyl isothiocyanate (7Me-IEITC) with anti-proliferative and pro-apoptotic effects on platinum-resistant human ovarian cancer cells

“…Isothiocyanates (ITC) represent a new class of suppressors of multi-drug resistance (MDR) in cancer. ITC such as phenethyl ITC (PEITC), benzyl ITC (BITC) and naphthyl ITC (NITC) have been reported to inhibit function of ABC efflux proteins, P-glycoproteins and other factors [3,4] implicated in emergence of MDR [5,6,7]. Further mechanisms of ITC activity in cancer prevention have been proposed, such as induction of G2/M cell-cycle arrest and apoptosis (8) or suppression of angiogenesis with a disruption of microtubulin polymerization and mitotic progression of endothelial cells [9,10].…”

Molecular Analysis of Therapy Resistance in Gastric Cancer

“…For this approach the complete panel of gastric tumor cells was continuously exposed to increasing temperatures and stable thermoresistant counterparts (EPG85-257P-TR, EPG85-257RDB-TR, EPG85-257RNOV-TR) of each gastric carcinoma cell line were selected [47,48]. In contrast to normal cell culture conditions at 37°C, the thermoresistant sublines continuously grow at 39.4°C, whereas the non-thermoresistant counterparts display growth inhibition at this temperature.…”

“…For this approach, various gastric carcinoma cell lines were exposed to stepwise-increased concentrations of different antineoplastic agents for several months resulting in the selection of drug-resistant gastric carcinoma sublines, respectively [39][40][41][42][43][44][45][46]. In analogy, thermoresistant gastric carcinoma cell lines were established by exposure to increasing temperatures [47,48]. An overview of published drug-resistant cell variants derived from gastric cancer is shown in table 1.…”

DUSP1 enhances the chemoresistance of gallbladder cancer via the modulation of the p38 pathway and DNA damage/repair system

“…Genes such as BCRP, MRP1, MDR1 and HIF1 were previously reported to be associated with drug-resistance in various cancer types were detected (28)(29)(30). DUSP1 expression was substantially elevated in the CDDP-resistant SGC996 cells compared with the normal SGC996 cells (Fig.…”