MULTICELLULAR-MEDIATED EXPRESSION OF P-GP AND MRP AND RELATIONSHIP WITH CELL CYCLE PROFILES IN HUMAN OVARIAN CANCER SK-OV-3ip1 MULTICELLULAR AGGREGATES

Clinical multidrug resistance to chemotherapeutic agents is a major obstacle to treatment of patients with advanced epithelial ovarian cancer. A number of possible mechanisms have been put forward to account for drug resistance1]. However, most of these proposed mechanisms are based largely on the study of drug-resistant variants isolated from tumor cell lines exposed to various classes of drugs in monolayer tissue culture. The impact of such mechanisms on clinical drug resistance remains spe…

Multicellular-mediated expression of P-GP and MRP and relationship with cell cycle profiles in human ovarian cancer SK-OV-3ip1 multicellular aggregates

Objective: To investigate the expression ofP-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. Methods: Liquid overlaysystem was employed to obtain multicellular aggregates. Expression of P-gp and MRP was detected with flowcytometry (FCM). Outer, intermediate and inner cellsfrom multicellular aggregates were collected bylayer-trypsinized method. Cell cycle profiles were also analyzed by FCM. Results: Compared with control cells, no expression of P-gp and MRP was detected inmonolyer cells (P=0.128 and P=0.604), but expression of P-gp and MRP in aggregate cells was significantlyelevated (P<0.01). P-gp expression in every layer cellswas also obviously increased (P<0.01). Furthermore,P-gp expression in every layer cells was also obviously increased (P=0.071). Tendency to increased G0-G1 phase and reduced S phase cells existed from outer throughintermediate to inner layers in multicellular aggregates but with no statistical difference. Cell percentages inG2-M phase also had no difference. However, compared with monolayer cells, cells in G0-G1 phase increased and cells in S and G2-M phases lowered significantly inevery layer and in the whole multicellular aggregates. Expression elevation of P-gp and MRP was consistent with increased G0-G1 percentage in aggregate cells.Conclusion: Expression of P-gp and MRP increases in cells of SK-OV-3ip1 multicellular aggregates and isconsistent with increased G0-G1 percentage, which implies the possible relationship between them and the possible role in multicellular-mediated drug resistance.