Resistance of human multidrug-resistant neoplastic cell lines to paclitaxel-induced-radiosensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833.
The non-immunosuppressive cyclosporine analog SDZ PSC 833 abolished the resistance of human multidrug resistant (MDR-1, P-gp) human promyelocyte leukemia HL-60/VCR cells in vitro to paclitaxel-induced cell cycle- and viability alterations, as well as resistance to paclitaxel-induced radiosensitization. Furthermore, SDZ PSC 833 abolished also the resistance of human multidrug-resistant ovarian A2780/ADR cells to paclitaxel-induced cell cycle alterations and reduced its resistance to paclitaxel-induced radiosensitization. In these multidrug-resistant ovarian carcinoma cells the supra-additive interaction between paclitaxel and SDZ PSC 833 pre-exposure and subsequent irradiation appeared at slightly higher paclitaxel concentrations (40-100 nM) compared to those required for a similar interaction in the parental drug sensitive A2780 cells (40-80 nM paclitaxel).
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.
J
J
Sedlak
L
L
Hunakova
M
M
Chorvath
M
M
Sulikova
L
L
Novotny
E
E
Boljesikova
R
R
Zeillinger
B
B
Chorvath
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000502:physiology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D005260:Female; D018922:HL-60 Cells / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D003524:Cyclosporins; D004273:DNA, Neoplasm; D010743:Phospholipids; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel; C070272:valspodar