XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
102.
MULTIDRUG RESISTANT P-GLYCOPROTEIN POSITIVE CELLS arE ALSO
CROSS-RESISTANT TO CISPLATIN
Lenka Gibalová 1 , Ján Sedlák 2 , Alena Reháková 1 , Martina Labudová 3 ,
Zdena Sulová 1 and Albert Breier 1
1
Institute of Molecular Physiology and Genetics SAS Bratislava, 2 Cancer Research
Institute SAS Bratislava, 3 Institute of Virology SAS Bratislava
P-glycoprotein (P-gp, a drug transporter of the plasma membrane) mediated multidrug
resistance of neoplastic cells represents a real problem in the chemotherapeutic treatment.
Mouse leukemia cells L1210 (S) and two drug resistant cell lines, in which the
overexpression of P-gp was induced by i. selection with vincristine (R) or by ii. transfection
of S cells with human gene for P-gp (T) are our experimental models. Cisplatin (cisPt)
is a substance untransportable by P-gp. We found that R and T cells are also resistant
to cisPt. However, cisPt resistance in R and T cells could not be reversed by verapamil
(known P-gp inhibitor), that excluding responsibility of P-gp transport activity for this
resistance. CisPt induced more pronounced entry to apoptosis in S cells than in R or T
cells. While similar levels of Bax and Bcl-2 proteins were observed in P-gp negative and
positive cells, cisPt induced a more significant decrease of the Bcl-2 levels in S cells than
in R and T cells. Consistent with this, cisPt induced a larger decrease of the Bcl-2 content
in the Bcl-2/Bax heterooligomer in S cells than in R cells. Moreover, cisPt induced
apoptotic DNA fragmentation was observed in all three cell sublines. All observations
indicated that expression of P-gp in L1210 cells is directly associated with reduction of
cisPt induced apoptosis and consequently with resistance to this drug that is not connected
with P-gp induced cisPt efflux.
Ackowledgement: This work was supported by: VVCE-0064-07, APVV-0084-07 and VEGA
2/0123/10, 2/0155/09.
XXII. Biochemistry Congress, Martin
227