11 research outputs found
Π ΠΎΠ»Ρ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π°ΡΡΠΎΡΠ°Π³ΠΈΠΈ Π² ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΈ ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ ΡΠ΅ΠΌΠΎΠ·ΠΎΠ»ΠΎΠΌΠΈΠ΄Π° Π½Π° ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π»ΠΈΠ½ΠΈΡΡ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ
Background. Despite advantages in treatment of metastatic melanoma it remains resistant to current therapy. Recent evidence indicates that tumor cells could overcome death through autophagy, a process that degrades cellular proteins and organelles to maintain cellular biosynthesis during nutrient deprivation or lack of energy. Objective: to investigate the involvement of autophagy inhibitors chloroquine (CQ) and LY-294.002 (LY) in temozolomide (TMZ) cytotoxicity in human melanoma cell lines.Materials and methods. The study was performed on patient-derived melanoma cell lines Mel Z, Mel IL and Mel MTP. The antiproliferative activity of combined TMZ and autophagy inhibitors treatment was determined by MTT assay and colony-forming assay. Cell cycle analysis, apoptosis activation and expression analysis of key autophagy markers under combined treatment was evaluated.Results. CQ and LY enhanced the cytotoxicity of TMZ and reduced colony formation in 3 melanoma cell lines, moreover both inhibitors increased cell population in G0 / G1 phase of cell cycle in Mel Z, Mel IL cell lines, but not in Mel MTP. CQ and LY synergistically activated apoptosis in all cell lines. The matrix RNA expression analysis of key autophagy genes showed autophagy involvement in enhanced cytotoxicity.Conclusions. Thus, autophagy inhibition on different stages of this process could overcome resistance to TMZ and be applicable as potent target in metastatic melanoma treatment.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠ΅ΡΠΌΠΎΡΡΡ Π½Π° ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ ΡΡΠΏΠ΅Ρ
ΠΈ Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ ΠΊΠΎΠΆΠΈ, ΡΡΠ° Π½ΠΎΠ·ΠΎΠ»ΠΎΠ³ΠΈΡ ΠΎΡΡΠ°Π΅ΡΡΡ ΠΊΡΠ°ΠΉΠ½Π΅ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΠΉ ΠΊ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΠΌ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌ. Π‘ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ ΠΌΠΎΠ³ΡΡ ΠΏΡΠ΅ΠΎΠ΄ΠΎΠ»Π΅Π²Π°ΡΡ Π³ΠΈΠ±Π΅Π»Ρ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ Π°ΡΡΠΎΡΠ°Π³ΠΈΠΈ β ΠΏΡΠΎΡΠ΅ΡΡΠ°, ΠΏΡΠΈ ΠΊΠΎΡΠΎΡΠΎΠΌ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ ΠΏΠ΅ΡΠ΅Π²Π°ΡΠΈΠ²Π°ΡΡ ΡΠ²ΠΎΠΈ ΡΠΎΠ±ΡΡΠ²Π΅Π½Π½ΡΠ΅ Π±Π΅Π»ΠΊΠΈ ΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΡ ΠΏΡΠΈ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΊΠ΅ ΡΠ½Π΅ΡΠ³ΠΈΠΈ ΠΈ Π΄Π΅ΡΠΈΡΠΈΡΠ΅ ΠΏΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΡΡ
Π²Π΅ΡΠ΅ΡΡΠ².Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² Π°ΡΡΠΎΡΠ°Π³ΠΈΠΈ, ΡΠ°ΠΊΠΈΡ
ΠΊΠ°ΠΊ Ρ
Π»ΠΎΡΠΎΠΊΠΈΠ½ (CQ) ΠΈ LY-294.002 (LY) Π½Π° ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ ΡΠ΅ΠΌΠΎΠ·ΠΎΠ»ΠΎΠΌΠΈΠ΄Π° (TMZ) Π² ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π»ΠΈΠ½ΠΈΡΡ
ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π Π°Π±ΠΎΡΠ° ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° Π½Π° ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π»ΠΈΠ½ΠΈΡΡ
ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ Mel Z, Mel IL ΠΈ Mel MTP, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΠΎΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΡΠΎΡ
ΠΎΠ΄ΠΈΠ²ΡΠΈΡ
Π»Π΅ΡΠ΅Π½ΠΈΠ΅ Π² Π ΠΠΠ¦ ΠΈΠΌ. Π. Π. ΠΠ»ΠΎΡ
ΠΈΠ½Π°. ΠΡΠ΅Π½ΠΊΡ Π°Π½ΡΠΈΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ TMZ Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ°ΠΌΠΈ Π°ΡΡΠΎΡΠ°Π³ΠΈΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π»ΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΠ’Π’-ΡΠ΅ΡΡΠ° ΠΈ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΊΠΎΠ»ΠΎΠ½ΠΈΠ΅ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ. ΠΡ ΠΎΡΠ΅Π½ΠΈΠ»ΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π°, Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ Π°ΠΏΠΎΠΏΡΠΎΠ·Π° ΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π°ΡΡΠΎΡΠ°Π³ΠΈΠΈ ΠΏΡΠΈ ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. CQ ΠΈ LY ΡΡΠΈΠ»ΠΈΠ²Π°Π»ΠΈ ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ TMZ ΠΈ ΡΠ½ΠΈΠΆΠ°Π»ΠΈ ΡΠΈΡΠ»ΠΎ ΠΆΠΈΠ·Π½Π΅ΡΠΏΠΎΡΠΎΠ±Π½ΡΡ
ΠΊΠΎΠ»ΠΎΠ½ΠΈΠΉ Π²ΠΎ Π²ΡΠ΅Ρ
ΠΈΠ·ΡΡΠ΅Π½Π½ΡΡ
Π»ΠΈΠ½ΠΈΡΡ
, ΠΏΡΠΈ ΡΡΠΎΠΌ ΠΎΠ±Π° ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π»ΠΈ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ ΠΏΠΎΠΏΡΠ»ΡΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π² ΡΡΠ°Π΄ΠΈΠΈ G0 / G1 Π² Π»ΠΈΠ½ΠΈΡΡ
Mel Z, Mel IL, Π½ΠΎ Π½Π΅ Π² Mel MTP. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ ΡΠ°ΠΊΠΆΠ΅, ΡΡΠΎ CQ ΠΈ LY ΡΠΈΠ½Π΅ΡΠ³ΠΈΡΠ½ΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π»ΠΈ Π°ΠΏΠΎΠΏΡΠΎΠ· Π²ΠΎ Π²ΡΠ΅Ρ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
Π»ΠΈΠ½ΠΈΡΡ
. ΠΠ½Π°Π»ΠΈΠ· ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΌΠ°ΡΡΠΈΡΠ½ΠΎΠΉ Π ΠΠ ΠΊΠ»ΡΡΠ΅Π²ΡΡ
Π³Π΅Π½ΠΎΠ² Π°ΡΡΠΎΡΠ°Π³ΠΈΠΈ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΠΎΠ²Π°Π» ΠΎ Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½ΠΈΠΈ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠ° Π² ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ½Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ Π°ΡΡΠΎΡΠ°Π³ΠΈΠΈ Π½Π° ΡΠ°Π·Π½ΡΡ
ΡΡΠ°ΠΏΠ°Ρ
Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠ° ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΏΡΠ΅ΠΎΠ΄ΠΎΠ»Π΅Π²Π°ΡΡ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡ ΠΊ TMZ ΠΈ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Π° ΠΊΠ°ΠΊ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½Π°Ρ ΠΌΠΈΡΠ΅Π½Ρ Π΄Π»Ρ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ
Gas-dynamic structure of a plasma jet in He and Ar, striking the surface of a liquid and a plane dielectric
The use of the modernized high-aperture shearing interferometer for visualization of flows
The role of autophagy inhibition in the enhanced cytotoxicity of temozolomide on melanoma cell lines
Background. Despite advantages in treatment of metastatic melanoma it remains resistant to current therapy. Recent evidence indicates that tumor cells could overcome death through autophagy, a process that degrades cellular proteins and organelles to maintain cellular biosynthesis during nutrient deprivation or lack of energy. Objective: to investigate the involvement of autophagy inhibitors chloroquine (CQ) and LY-294.002 (LY) in temozolomide (TMZ) cytotoxicity in human melanoma cell lines.Materials and methods. The study was performed on patient-derived melanoma cell lines Mel Z, Mel IL and Mel MTP. The antiproliferative activity of combined TMZ and autophagy inhibitors treatment was determined by MTT assay and colony-forming assay. Cell cycle analysis, apoptosis activation and expression analysis of key autophagy markers under combined treatment was evaluated.Results. CQ and LY enhanced the cytotoxicity of TMZ and reduced colony formation in 3 melanoma cell lines, moreover both inhibitors increased cell population in G0 / G1 phase of cell cycle in Mel Z, Mel IL cell lines, but not in Mel MTP. CQ and LY synergistically activated apoptosis in all cell lines. The matrix RNA expression analysis of key autophagy genes showed autophagy involvement in enhanced cytotoxicity.Conclusions. Thus, autophagy inhibition on different stages of this process could overcome resistance to TMZ and be applicable as potent target in metastatic melanoma treatment