REGULATION OF EXPRESSION OF P-GLYCOPROTEIN AND GST BY MULTIDRUG-RESISTANT REVERSORS IN ADM-SENSITIVE AND ADM-RESISTANT HUMAN TUMOR CELL LINES
Abstract
Objective: To investigate the regulation of pglycoprotein (PgP) and GST expression from three reversors in ADM-sensitive and ADM-resistant human leukemic cell lines and KB cell lines.
Methods: Immunocytochemical(ICC) technique was applied to detect the multidrug-resistant gene products, PgP and GST in K562 cells, K562/ADM cells and KB cells before or after treatment with three resistant reversors, i.e., verapamil(VER), dipyriamole(DPM) and cyclosporin A(CsA).
Results: PgP expression was observed in K562/ADM cells but not in K562 cells or KB cells, and GSTPI expression, in KB cells but not in K562 cells or K562/ADM cells. Overexpressions of PgP were induced after treatment with VER, or DPM or CsA for 24 h in K562 cells but not KB cells. DPM-treated K562/ADM cells expressed PgP much lower than DPM-free K562/ADM cells. PgP was not detectable after treatment of K562/ADM cells with CsA for 24 h. Induced GSTPI expression was found after treatment with DPM, but not VER or CsA in K562 cells. No significant difference was observed for GSTPI expresion in KB cells before and after treatment with VER, or DPM, or CsA.
Conclusion: The findings suggested that reversal activity of some drug resistant reversors, such as VER, DPM, CsA, may be declined by themselves through induction of PgP, perhaps GST.
Methods: Immunocytochemical(ICC) technique was applied to detect the multidrug-resistant gene products, PgP and GST in K562 cells, K562/ADM cells and KB cells before or after treatment with three resistant reversors, i.e., verapamil(VER), dipyriamole(DPM) and cyclosporin A(CsA).
Results: PgP expression was observed in K562/ADM cells but not in K562 cells or KB cells, and GSTPI expression, in KB cells but not in K562 cells or K562/ADM cells. Overexpressions of PgP were induced after treatment with VER, or DPM or CsA for 24 h in K562 cells but not KB cells. DPM-treated K562/ADM cells expressed PgP much lower than DPM-free K562/ADM cells. PgP was not detectable after treatment of K562/ADM cells with CsA for 24 h. Induced GSTPI expression was found after treatment with DPM, but not VER or CsA in K562 cells. No significant difference was observed for GSTPI expresion in KB cells before and after treatment with VER, or DPM, or CsA.
Conclusion: The findings suggested that reversal activity of some drug resistant reversors, such as VER, DPM, CsA, may be declined by themselves through induction of PgP, perhaps GST.