Overcoming High Trabectedin Resistance of Soft-tissue Sarcoma With Recombinant Methioninase: A Potential Solution of a Recalcitrant Clinical Problem.
Anticancer Res
; 44(9): 3785-3791, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39197928
ABSTRACT
BACKGROUND/AIM:
Drug resistance has been a recalcitrant problem for sarcoma patients for many decades. Trabectedin is a second-line chemotherapy for soft-tissue sarcoma that often leads to resistance and death of the patients. The objective of the present study was to address the issue of trabectedin-chemoresistance in HT1080 fibrosarcoma cells by combining recombinant methioninase (rMETase) with trabectedin and examining their efficacy on trabectedin-resistant fibrosarcoma cells in vitro. MATERIALS ANDMETHODS:
Trabectedin-resistant HT1080 (TR-HT1080) cells were generated by subjecting HT1080 human fibrosarcoma cells to increasing trabectedin concentrations (3.3-8 nM). IC50 values for trabectedin and rMETase were compared for HT1080 and TR-HT1080 cells. TR-HT 1080 cells were placed into four groups to determine synergy of rMETase and trabectedin on TR-HT1080 cells a control group with no treatment; a group treated with trabectedin (3.3 nM); a group treated with rMETase (0.75 U/ml); and a group treated with both trabectedin (3.3 nM) and rMETase (0.75 U/ml).RESULTS:
The IC50 value of trabectedin- on TR-HT1080 cells was 42.9 nM, whereas the IC50 value of trabectedin on the parental HT1080 cells was 3.3 nM, indicating a 13-fold increase. The combination of rMETase (0.75 U/ml) and trabectedin (3.3 nM) was synergistic on TR-HT1080 cells resulting in an inhibition of 64.2% compared to trabectedin alone (5.7%) or rMETase alone (50.5%) (p<0.05). rMETase increased the efficacy of trabectedin 11-fold on trabectedin-resistant fibrosarcoma cells.CONCLUSION:
The combined administration of trabectedin and rMETase was synergistic on the viability of TR-HT1080 cells in vitro. The combination of rMETase and trabectedin has promising clinical potential for overcoming chemo-resistance of soft-tissue sarcoma.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Liasas de Carbono-Azufre
/
Proteínas Recombinantes
/
Resistencia a Antineoplásicos
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Antineoplásicos Alquilantes
/
Tetrahidroisoquinolinas
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Dioxoles
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Trabectedina
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Grecia