Tumor Recurrence and Drug Resistance Properties of Side Population Cells in High Grade Ovary Cancer

Abstract

Our data suggest that ovarian cancer contain small sub-population of side population cells which shares some characteristics of stem cells. The co-expression of ABC transporters and stem cells surface markers in SP cells may associate with resistance to chemotherapeutic agents, apoptosis and also supports a role for these cells in tumor recurrence, metastasis and invasion.

Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL‑60 cells with tolerance to arsenic trioxide and contribution of leukemia stem cells

“…MDR is currently a major and unresolved impediment to leukemia therapy (1)(2)(3)10). Although numerous extensive studies have investigated leukemia drug-resistance, regulatory pathways and intervention measures, the underlying mechanisms remain to be fully understood and few effective or clinically practical countermeasures have been identified (23)(24)(25).…”

“…As 2 O 3 has good curative effects and little cross-resistance with conventional chemotherapeutics (2,(17)(18)(19)(20)(21). Previous studies have revealed that conventional MDR leukemia cells exhibit increased sensitivity to As 2 O 3 instead of manifesting cross-resistance.…”

“…One potential explanation for this is that As 2 O 3 may not be a substrate of P-gp and may inhibit P-gp activity (2,(18)(19)(20)(21)(22). The present study selected HL-60 human promyelocyte leukemia cells for doxorubicin (ADM)-resistance by long-term exposure to intermittent and continuous stepwise increments of ADM, and characterized the distinguishing features of acquired MDR, particularly in terms of sensitivity to As 2 O 3 and the role of LSCs.…”

“…However, chemotherapy-induced multidrug resistance (MDR) frequently induces therapy failure or tumor recurrence (1)(2)(3). MDR involves various mechanisms including, adenosine triphosphate-binding cassette (ABC) transporters, P-glycoprotein (P-gp), multidrug-resistance-related protein (MRP) and breast-cancer-resistance protein (BCRP) overexpression, which function to efflux certain molecules out of the cells (4)(5)(6)(7)(8).…”

“…Numerous previous studies have confirmed that the rare LSC sub-population in leukemia has self-renewal abilities, uncommitted proliferative capacities, relative dormancy or quiescence, high expression of ABC transporters and good DNA-damage repair ability (9)(10)(11)(12). In addition, LSCs have strong resistance to almost all chemotherapeutics (2,5). However, the role of LSCs and the mechanism underlying transmission of super-drug resistance to daughter cells remains unclear.…”