Π Π΅Π³ΡΠ»ΡΡΠΎΡΠ½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ 17 ?-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° ΠΈ 1, 25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΡΠ°ΠΊΠΎΠ²ΡΡ Π»ΠΈΠ½ΠΈΠΉ
Π Π°ΠΊΠΈ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΡΠ°ΠΊΠΆΠ΅ ΡΠ²Π»ΡΡΡΡΡ Π²Π΅ΡΡΠΌΠ° ΡΠ°ΡΡΡΠΌ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ΠΌ. Π ΡΠ°Π·Π²ΠΈΡΡΡ ΡΡΡΠ°Π½Π°Ρ ΡΠ°ΠΊ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Π·Π°Π½ΠΈΠΌΠ°Π΅Ρ ΠΏΠ΅ΡΠ²ΠΎΠ΅ ΠΈΠ»ΠΈ Π²ΡΠΎΡΠΎΠ΅ ΠΌΠ΅ΡΡΠΎ ΠΏΠΎ ΡΠ°ΡΡΠΎΡΠ΅ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Ρ ΠΆΠ΅Π½ΡΠΈΠ½ (20β25% Π²ΡΠ΅Ρ ΡΠ»ΡΡΠ°Π΅Π²) (Π’ΡΠ°ΠΏΠ΅Π·Π½ΠΈΠΊΠΎΠ², ΠΠΊΡ Π°ΡΠ΄Ρ, 1981). Π ΠΏΡΠΎΡΠΈΠ²ΠΎΠΏΠΎΠ»ΠΎΠΆΠ½ΠΎΡΡΡ l, 25(OH)2D3, 17Ρ-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ» ΡΡΠΈΠΌΡΠ»ΠΈΡΡΠ΅Ρ ΠΏΡΠΎΡΠ΅ΡΡΡ Π²ΠΎ ΠΌΠ½ΠΎΠ³ΠΈΡ ΡΠ°ΠΊΠΎΠ²ΡΡ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π»ΠΈΠ½ΠΈΡΡ , Π² ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΠΏΡΠΈ ΡΠ°ΠΊΠ΅ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
- Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΡΠ΄Π΅ΡΠΆΠΊΠ°
- ΠΠΈΡΠ΅ΡΠ°ΡΡΡΠ°
- ΠΡΡΠ³ΠΈΠ΅ ΡΠ°Π±ΠΎΡΡ
- ΠΠΎΠΌΠΎΡΡ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΠ»Π°Π²Π° 1. ΠΠΠΠΠ ΠΠΠ’ΠΠ ΠΠ’Π£Π Π«
- 1. 1. ΠΡΡΡΠΎΠ³Π΅Π½ΠΎΠ²ΡΠΉ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ ΠΈ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π°
- 1. 2. ΠΠΈΡΠ°ΠΌΠΈΠ½ D3 ΠΈ Π΅Π³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ
- 1. 3. ΠΠ΅Π½ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° ΠΊΠ΅ΡΠ°ΡΠΈΠ½ΠΎΡΠΈΡΠΎΠ² — ΠΏΡΠ΅Π΄ΡΡΠ°Π²ΠΈΡΠ΅Π»Ρ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Π³Π΅Π½ΠΎΠ² ΡΠ°ΠΊΡΠΎΡΠΎΠ² ΡΠΎΡΡΠ° ΡΠΈΠ±ΡΠΎΠ±Π»Π°ΡΡΠΎΠ²
- 1. 4. Π‘Π΅ΠΌΠ΅ΠΉΡΡΠ²ΠΎ ΠΏΡΠΎΡΠ΅ΠΈΠ½-ΠΊΠΈΠ½Π°Π· ΠΈ ΠΠΠ -ΠΊΠΈΠ½Π°Π·
- ΠΠ»Π°Π²Π° 2. ΠΠΠ’ΠΠ ΠΠΠΠ« Π ΠΠΠ’ΠΠΠ«
- 2. 1. ΠΠ°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ ΡΡΠ°ΠΌΠΌΡ ΠΈ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Ρ
- 2. 2. ΠΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΠΊΡΠ»ΡΡΡΡΡ ΠΈ Π²ΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ Π ΠΠ
- 2. 3. ΠΡΠ΅Π½ΠΊΠ° ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΠΎΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ
- 2. 4. ΠΡΠΈΠ³ΠΎΡΠΎΠ²Π»Π΅Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ Π»ΠΈΠ·Π°ΡΠ°
- 2. 5. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠ° ΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΡ
- 2. 6. ΠΠΈΠΊΡΠΎΡΠΈΠΏΠΎΠ²ΡΠΉ Π°Π½Π°Π»ΠΈΠ·
- 2. 7. ΠΠ΅ΡΡΠ΅ΡΠ½-Π±Π»ΠΎΡ-Π°Π½Π°Π»ΠΈΠ·
- 2. 8. Π Π΅Π²Π΅ΡΡΠ°Π·Π½ΠΎ-ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½Π°Ρ ΡΠ΅Π°ΠΊΡΠΈΡ
- 2. 9. ΠΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½Π°Ρ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½Π°Ρ ΡΠ΅ΠΏΠ½Π°Ρ ΡΠ΅Π°ΠΊΡΠΈΡ Π² ΡΠ΅Π°Π»ΡΠ½ΠΎΠΌ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ
- 2. 10. ΠΠ»ΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ° Π² ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½ΡΠΉ Π²Π΅ΠΊΡΠΎΡ PGEM-T Easy
- 2. 11. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Ρ
- 2. 12. Π‘ΠΈΠΊΠ²Π΅Π½Ρ
- 2. 13. ΠΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΠΠ -ΠΊΠΈΠ½Π°Π·Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ
- 2. 14. ΠΠ΅ΡΠΎΠ΄ Π°Π½Π°Π»ΠΈΠ·Π° Π ΠΠ ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ Π·Π°ΡΠΈΡΡ ΠΎΡ ΡΠ°ΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΡ Π ΠΠΠ°Π·Π°ΠΌΠΈ
- 2. 15. ΠΡΠΎΠ³ΡΠ°ΠΌΠΌΠ½ΠΎΠ΅ ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΈ Π±Π°Π·Ρ Π΄Π°Π½Π½ΡΡ
- 2. 16. Π Π΅Π°ΠΊΡΠΈΠ²Ρ ΠΈ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ
- ΠΠ»Π°Π²Π° 3. Π ΠΠΠ£ΠΠ¬Π’ΠΠ’Π«
- 3. 1. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π³Π΅Π½Π°
- /"17Π -ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»ΠΎΠΌ ΠΈ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½ΠΎΠΌ D
- 3. 1. 1. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° Π²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π»ΠΈΠ½ΠΈΠΈ MCF
- 3. 1. 2. ΠΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ Π² 5"-ΡΠ»Π°Π½ΠΊΠΈΡΡΡΡΠ΅ΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ Π³Π΅Π½Π° kgf
- 3. 1. 3. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΌΠΈΠΊΡΠΎΡΠΈΠΏΠΎΠ²ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°
- 3. 1. 4. ΠΡΠ΅Π½ΠΊΠ° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΠΠ ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠΈ Π ΠΠ Π³Π΅Π½ΠΎΠΌ kgf ΠΏΠΎΠ΄ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 ΠΈ 17Π -ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π°
- 3. 1. 5. ΠΠ΅ΡΡΠ΅ΡΠ½-Π±Π»ΠΎΡ-Π°Π½Π°Π»ΠΈΠ· ΡΡΠΎΠ²Π½Π΅ΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³Π΅Π½Π° kgf Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π»ΠΈΠ½ΠΈΠΉ MCF7 ΠΈ LNCaP
- 3. 2. ΠΠ»ΠΈΡΠ½ΠΈΠ΅ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 ΠΈ 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° Π½Π° ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ ΡΠ°ΠΊΠΎΠ²ΡΡ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π»ΠΈΠ½ΠΈΠΉ ΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ ΠΠΠ -ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°
- 3. 2. 1. ΠΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΉ MCF7 ΠΈ LNCaP Π²ΠΎΠ·ΡΠ°ΡΡΠ°Π΅Ρ ΠΏΠΎΠ΄ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ 17Ρ-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° ΠΈ ΡΠΎΡΠΌΠΎΠ·ΠΈΡΡΡ ΠΏΠΎΠ΄ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D
- 3. 2. 2. ΠΡΠ°ΡΠΊΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡ 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° ΠΈ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 Π°ΠΊΡΠΈΠ²ΠΈΡΡΡΡ ΠΠΠ -ΠΊΠΈΠ½Π°Π·Ρ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
- MCF7 ΠΈ LNCaP
- 3. 2. 3. ΠΠ»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 ΠΏΠΎΠ΄Π°Π²Π»ΡΠ΅Ρ 17Π -ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»-Π·Π°Π²ΠΈΡΠΈΠΌΡΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΠΠ -ΠΊΠΈΠ½Π°Π· Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π»ΠΈΠ½ΠΈΠΈΠΈ LNCaP
- ΠΠΠ‘Π£ΠΠΠΠΠΠ
- ΠΠ«ΠΠΠΠ«
Π Π΅Π³ΡΠ»ΡΡΠΎΡΠ½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ 17 ?-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° ΠΈ 1, 25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΡΠ°ΠΊΠΎΠ²ΡΡ Π»ΠΈΠ½ΠΈΠΉ (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
ΠΠΈΠ³Π°Π½Π΄Ρ ΡΠ΄Π΅ΡΠ½ΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² — ΡΡΠΎ Π½Π΅Π±ΠΎΠ»ΡΡΠΈΠ΅ Π»ΠΈΠΏΠΎΡΠΈΠ»ΡΠ½ΡΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ, ΠΊΠΎΡΠΎΡΡΠ΅ Π±Π΅ΡΠΏΡΠ΅ΠΏΡΡΡΡΠ²Π΅Π½Π½ΠΎ ΠΏΡΠΎΠ½ΠΈΠΊΠ°ΡΡ ΡΠ΅ΡΠ΅Π· ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ ΠΈ ΡΠ΄Π΅ΡΠ½ΡΡ ΠΌΠ΅Π±ΡΠ°Π½Ρ, ΠΈ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΡΡ ΡΠΎ ΡΠ²ΠΎΠΈΠΌΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌΠΈ, Π»ΠΎΠΊΠ°Π»ΠΈΠ·ΠΎΠ²Π°Π½Π½ΡΠΌΠΈ Π² ΡΠ΄ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ (Beato et al., 1995; Mangelsdorf et al., 1995; Perlman, Evans- 1997). ΠΠΈΠ³Π°Π½Π΄, ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΡ Ρ Π±Π΅Π»ΠΊΠΎΠΌ (ΡΠ΄Π΅ΡΠ½ΡΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ), ΠΏΠ΅ΡΠ΅Π²ΠΎΠ΄ΠΈΡ Π΅Π³ΠΎ Π² Π°ΠΊΡΠΈΠ²Π½ΡΡ ΡΠΎΡΠΌΡ (Sone et al., 1989; Hughes et al., 1991). ΠΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠ΄Π΅ΡΠ½ΡΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡ, ΠΊΠ°ΠΊ Π² ΡΠΎΡΠΌΠ΅ ΠΌΠΎΠ½ΠΎΠΌΠ΅ΡΠ½ΡΡ , ΡΠ°ΠΊ ΠΈ Π΄ΠΈΠΌΠ΅ΡΠ½ΡΡ ΡΡΡΡΠΊΡΡΡ, ΠΏΡΠΈΠΎΠ±ΡΠ΅ΡΠ°ΡΡ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΡΡ Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡΠΌΠΈ ΠΠΠ, ΠΈΠΌΠ΅ΡΡΠΈΠΌΠΈ Π² ΡΠ²ΠΎΠ΅ΠΌ ΡΠΎΡΡΠ°Π²Π΅ ΠΏΠΎΠ΄ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ AGGTCA ΠΈ Π΅Π΅ Π²Π°ΡΠΈΠ°ΡΠΈΠΈ, Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΡΠ΅ Π΄Π»Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠ² Π³Π΅Π½ΠΎΠ² (Umensono et al., 1991; Mangelsdorf et al., 1995). Π’Π°ΠΊΠΎΠ³ΠΎ ΡΠΎΠ΄Π° ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ Π»ΠΎΠΊΠ°Π»ΠΈΠ·ΠΎΠ²Π°Π½Ρ Π² ΠΈΠ½ΡΡΠΎΠ½Π°Ρ ΠΈ 5'- ΡΠ»Π°Π½ΠΊΠΈΡΡΡΡΠΈΡ ΠΎΠ±Π»Π°ΡΡΡΡ Π³Π΅Π½ΠΎΠ² (Koop, Hood, 1994). ΠΠΎΡΠ»Π΅ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΡΠ΄Π΅ΡΠ½ΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² Ρ ΠΠΠ, ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Π΅ΠΉ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ ΠΌΠ ΠΠ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ Π·Π° ΡΡΠ΅Ρ ΠΏΡΡΠΌΠΎΠ³ΠΎ ΠΈΠ»ΠΈ ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΎΠΊ-Π±Π΅Π»ΠΊΠΎΠ²ΠΎΠ³ΠΎ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Ρ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΡΠΌ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠΌ, Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΅Π³ΠΎ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ ΠΈΠ»ΠΈ ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Π΅ΠΉ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ ΠΌΠ ΠΠ ΠΈ, ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ, ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠΈ Π±Π΅Π»ΠΊΠ°, ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΠΎΠ³ΠΎ ΡΠ΅ΠΌ ΠΈΠ»ΠΈ ΠΈΠ½ΡΠΌ Π³Π΅Π½ΠΎΠΌ Π² ΠΊΠ»Π΅ΡΠΊΠ΅ (Gronemeyer, Laudet, 1995; Mangelsdorf et al., 1995). ΠΡΠ΅ ΡΠ΄Π΅ΡΠ½ΡΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡ ΠΈΠΌΠ΅ΡΡ ΡΡ ΠΎΠΆΡΡ Π΄ΠΎΠΌΠ΅Π½Π½ΡΡ ΡΡΡΡΠΊΡΡΡΡ Π±Π΅Π»ΠΊΠΎΠ²ΠΎΠΉ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ ΠΈ ΠΏΠΎ ΡΡΠΎΠΌΡ ΠΏΡΠΈΠ·Π½Π°ΠΊΡ ΠΎΠ±ΡΠ΅Π΄ΠΈΠ½Π΅Π½Ρ Π² ΠΎΠ΄Π½ΠΎ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²ΠΎ (Mangelsdorf et al., 1995).
ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² ΠΈ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠΎΠ² Π²Π»ΠΈΡΠ½ΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ΡΠ΄Π΅ΡΠ½ΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΠΈ ΡΠ°ΠΌΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² ΡΡΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² Π½Π° ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠ΅ ΠΊΠ°ΡΠΊΠ°Π΄Ρ ΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ Π³Π΅Π½ΠΎΠ² ΡΠ²Π»ΡΠ΅ΡΡΡ Π²Π°ΠΆΠ½ΡΠΌ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ Π² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΡ ΠΊΠ°Π½ΡΠ΅ΡΠΎΠ³Π΅Π½Π΅Π·Π°. ΠΠ΄Π½ΠΈΠΌ ΠΈΠ· ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΡΠΈΡ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² ΡΠ²Π»ΡΠ΅ΡΡΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠ΄Π΅ΡΠ½ΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π½ΡΠΌΠΈ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡΠΌΠΈ ΠΠΠ, Π½Π°Π·ΡΠ²Π°Π΅ΠΌΡΠΌΠΈ Π³ΠΎΡΠΌΠΎΠ½-Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΠΌΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ°ΠΌΠΈ (HRE) (Pabo, Sauer, 1994).
ΠΠ΄Π½ΠΈΠΌ ΠΈΠ· ΠΏΠΎΠ΄Ρ ΠΎΠ΄ΠΎΠ² ΠΊ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π³ΠΎΡΠΌΠΎΠ½ΠΎΠ² ΠΈ Π³ΠΎΡΠΌΠΎΠ½ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ, ΠΈΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡΡΠΈΡ , Π΄Π»Ρ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΡ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ ΡΠ°ΠΊΠΎΠ²ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΡ ΠΏΡΡΡΡ ΠΈ ΡΡΠΎΠ²Π½ΡΡ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ Π³Π΅Π½ΠΎΠ² Ρ ΠΏΠΎΠΌΠΎΡΡΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² Π±Π΅Π»ΠΊΠΎΠ² ΡΠ΄Π΅ΡΠ½ΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² (Resche-Rigon, Gronemeyer, 1998).
Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΡΡΡΡΡ Π½Π΅ΠΊΠΎΡΠΎΡΡΠ΅ Π°ΡΠΏΠ΅ΠΊΡΡ Π³Π΅Π½ΠΎΠΌΠ½ΠΎΠ³ΠΎ ΠΈ Π½Π΅ Π³Π΅Π½ΠΎΠΌΠ½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ΡΠ΄Π΅ΡΠ½ΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² — 17Π ~ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° ΠΈ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 (l, 25(OH)2D3) Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π»ΠΈΠ½ΠΈΠΉ LNCaP ΠΈ MCF7 (ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ, ΡΠ°ΠΊΠ° ΠΏΡΠΎΡΡΠ°ΡΡ ΠΈ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ).
Π Π°ΠΊ ΠΏΡΠΎΡΡΠ°ΡΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠ΄Π½ΠΈΠΌ ΠΈΠ· Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΡΡ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΉ Ρ ΠΌΡΠΆΡΠΈΠ½ ΠΈ ΡΡΠΎΠΈΡ Π½Π° Π²ΡΠΎΡΠΎΠΌ ΠΌΠ΅ΡΡΠ΅ ΠΏΠΎΡΠ»Π΅ ΡΠ°ΠΊΠ° Π»Π΅Π³ΠΊΠΈΡ Π² ΡΡΠ΄Ρ ΠΏΡΠΈΡΠΈΠ½ ΡΠΌΠ΅ΡΡΠ½ΠΎΡΡΠΈ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ (Ficazzola, Taneja, 1997). ΠΡΠ»Π° ΠΏΠΎΠΊΠ°Π·Π°Π½Π° ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΡ ΡΡΠΎΠ²Π½Ρ Π²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 Π² ΡΡΠ²ΠΎΡΠΎΡΠΊΠ΅ ΠΊΡΠΎΠ²ΠΈ Ρ ΡΠΈΡΠΊΠΎΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΡΠ°ΠΊΠΎΠΌ ΠΏΡΠ΅Π΄ΡΡΠ°ΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ: ΠΌΡΠΆΡΠΈΠ½Ρ Ρ ΠΏΠΎΠ½ΠΈΠΆΠ΅Π½Π½ΡΠΌ ΡΡΠΎΠ²Π½Π΅ΠΌ Π²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 (Π½ΠΈΠΆΠ΅ 50 Π½ΠΌ/Π») ΠΈΠΌΠ΅ΡΡ Π² 1.7 ΡΠ°Π·Π° Π±ΠΎΠ»ΡΡΠΈΠΉ ΡΠΈΡΠΊ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΡΠ°ΠΊΠΎΠΌ ΠΏΡΠΎΡΡΠ°ΡΡ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΌΡΠΆΡΠΈΠ½Π°ΠΌΠΈ, Ρ ΠΊΠΎΡΠΎΡΡΡ ΡΡΠΎΠ²Π΅Π½Ρ 25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 Π²ΡΡΠ΅ ΡΡΠ΅Π΄Π½Π΅Π³ΠΎ (Frick et al., 1987; Tuohimaa et al., 2001).
Π Π°ΠΊΠΈ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΡΠ°ΠΊΠΆΠ΅ ΡΠ²Π»ΡΡΡΡΡ Π²Π΅ΡΡΠΌΠ° ΡΠ°ΡΡΡΠΌ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ΠΌ. Π ΡΠ°Π·Π²ΠΈΡΡΡ ΡΡΡΠ°Π½Π°Ρ ΡΠ°ΠΊ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Π·Π°Π½ΠΈΠΌΠ°Π΅Ρ ΠΏΠ΅ΡΠ²ΠΎΠ΅ ΠΈΠ»ΠΈ Π²ΡΠΎΡΠΎΠ΅ ΠΌΠ΅ΡΡΠΎ ΠΏΠΎ ΡΠ°ΡΡΠΎΡΠ΅ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Ρ ΠΆΠ΅Π½ΡΠΈΠ½ (20−25% Π²ΡΠ΅Ρ ΡΠ»ΡΡΠ°Π΅Π²) (Π’ΡΠ°ΠΏΠ΅Π·Π½ΠΈΠΊΠΎΠ², ΠΠΊΡ Π°ΡΠ΄Ρ, 1981). Π ΠΏΡΠΎΡΠΈΠ²ΠΎΠΏΠΎΠ»ΠΎΠΆΠ½ΠΎΡΡΡ l, 25(OH)2D3, 17Ρ-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ» ΡΡΠΈΠΌΡΠ»ΠΈΡΡΠ΅Ρ ΠΏΡΠΎΡΠ΅ΡΡΡ Π²ΠΎ ΠΌΠ½ΠΎΠ³ΠΈΡ ΡΠ°ΠΊΠΎΠ²ΡΡ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π»ΠΈΠ½ΠΈΡΡ , Π² ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΠΏΡΠΈ ΡΠ°ΠΊΠ΅ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ, ΠΈ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΠ΅ Π΅Π³ΠΎ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ², ΡΡΠ΅Π΄ΠΈ ΠΊΠΎΡΠΎΡΡΡ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ΅ ΠΌΠ΅ΡΡΠΎ Π·Π°Π½ΠΈΠΌΠ°Π΅Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π°Π½ΡΠΈΡΡΡΡΠΎΠ³Π΅Π½ΠΎΠ², ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΠ΅Ρ Π·Π°ΠΌΠ΅Π΄Π»Π΅Π½ΠΈΡ ΡΠΎΡΡΠ° Π³ΠΎΡΠΌΠΎΠ½-Π·Π°Π²ΠΈΡΠΈΠΌΡΡ ΠΎΠΏΡΡ ΠΎΠ»Π΅ΠΉ (Santen et al., 1990). ΠΠΏΠ΅ΡΠ²ΡΠ΅ ΡΡΡΠ΅ΠΊΡ 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° Π±ΡΠ» ΠΎΠΏΠΈΡΠ°Π½ Π² ΡΠ°Π±ΠΎΡΠ΅ ΠΠΈΠΏΠΏΠΌΠ°Π½Π° ΠΈ ΠΠΎΠ»Π°Π½Π° (Lippman, Bolan, 1975). ΠΡΠΈ Π°Π²ΡΠΎΡΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½Π½ΡΠΉ Π°Π½ΡΠΈΡΡΡΡΠΎΠ³Π΅Π½ΠΎΠΌ ΡΠ°ΠΌΠΎΠΊΡΠΈΡΠ΅Π½ΠΎΠΌ ΡΠΎΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ MCF7 — ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ (ΡΡΡΡΠΎΠ³Π΅Π½-ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΠΎΠΉ) Π²ΠΎΠ·ΠΎΠ±Π½ΠΎΠ²Π»ΡΠ»ΡΡ ΠΏΡΠΈ Π΄ΠΎΠ±Π°Π²Π»Π΅Π½ΠΈΠΈ 17[3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π°. Π‘ ΡΠ΅Ρ ΠΏΠΎΡ Π±ΡΠ»ΠΎ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π² ΡΡΠΎΠΌ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠΈ.
Π ΡΠ°Π±ΠΎΡΠ΅ ΠΏΠΎΠ΄ΡΠΎΠ±Π½ΠΎ ΠΎΠΏΠΈΡΡΠ²Π°Π΅ΡΡΡ Π΄ΠΎΠΌΠ΅Π½Π½Π°Ρ ΡΡΡΡΠΊΡΡΡΠ°, ΡΡΠ½ΠΊΡΠΈΠΈ ΠΈ Π±ΠΈΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° Π±Π΅Π»ΠΊΠΎΠ² ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° ΡΠ΄Π΅ΡΠ½ΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² (Π½Π° ΠΏΡΠΈΠΌΠ΅ΡΠ΅ 17Π -ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π°) ΠΈ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡΡΡ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ l, 25(OH)2D3 ΠΊΠ°ΠΊ ΠΏΡΠ΅Π΄ΡΡΠ°Π²ΠΈΡΠ΅Π»Ρ ΡΡΠΎΠ³ΠΎ ΠΆΠ΅ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π°. ΠΠΏΠΈΡΡΠ²Π°ΡΡΡΡ ΡΠ°ΠΊΠΆΠ΅ ΡΠ°ΠΊΡΠΎΡ ΡΠΎΡΡΠ° ΠΊΠ΅ΡΠ°ΡΠΈΠ½ΠΎΡΠΈΡΠΎΠ² ΠΈ ΠΌΠΈΡΠΎΠ³Π΅Π½-Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΠ΅ ΠΏΡΠΎΡΠ΅ΠΈΠ½-ΠΊΠΈΠ½Π°Π·Ρ, ΠΏΠΎΡΠΊΠΎΠ»ΡΠΊΡ ΠΎΠ½ΠΈ ΡΠ²Π»ΡΡΡΡΡ ΠΎΡΠ½ΠΎΠ²Π½ΡΠΌΠΈ ΠΌΠΈΡΠ΅Π½ΡΠΌΠΈ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ 1,25(OH)2D3h 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π°, ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΠΎΠ³ΠΎ Π² Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅.
Π¦Π΅Π»Ρ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ Π·Π°ΠΊΠ»ΡΡΠ°Π»Π°ΡΡ Π² ΡΠΎΠΌ, ΡΡΠΎΠ±Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ l, 25(OH)2D3 ΠΈ 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° Π½Π° ΠΊΠ»Π΅ΡΠΊΠΈ Π»ΠΈΠ½ΠΈΠΈ ΡΠ°ΠΊΠ° Π³ΡΡΠ΄ΠΈ ΠΈ ΡΠ°ΠΊΠ° ΠΏΡΠΎΡΡΠ°ΡΡ, ΠΈ Π²ΡΡΠ²ΠΈΡΡ ΠΈΡ ΡΡΠ°ΡΡΠΈΠ΅ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π³Π΅Π½Π° ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° ΠΊΠ΅ΡΠ°ΡΠΈΠ½ΠΎΡΠΈΡΠΎΠ² (kg/), Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π° Π½Π΅ΠΊΠΎΡΠΎΡΡΠ΅ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΡ ΠΠΠ -ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ ΠΏΡΡΠΈ.
Π ΡΠ°Π±ΠΎΡΠ΅ Π±ΡΠ»ΠΈ ΠΏΠΎΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ»Π΅Π΄ΡΡΡΠΈΠ΅ Π·Π°Π΄Π°ΡΠΈ:
1. ΠΡΡΠ²ΠΈΡΡ ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊ Π²Π»ΠΈΡΠ½ΠΈΠ΅ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 ΠΈ 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° Π½Π° ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ Π³Π΅Π½Π° ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° ΠΊΠ΅ΡΠ°ΡΠΈΠ½ΠΎΡΠΈΡΠΎΠ² (kgf), Π° ΡΠ°ΠΊΠΆΠ΅ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° Π²ΠΈΡΠ°ΠΌΠΈΠ½Π° D Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ (Π»ΠΈΠ½ΠΈΠΈ MCF7).
2. ΠΠ°ΠΉΡΠΈ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠ΅ ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ (HRE) Π² 5'-ΡΠ»Π°Π½ΠΊΠΈΡΡΡΡΠ΅ΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ Π³Π΅Π½Π° kgf Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΊΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΡΡ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌ ΠΈ Π±Π°Π· Π΄Π°Π½Π½ΡΡ .
3. ΠΠ·ΡΡΠΈΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ l, 25(OH)2D3 ΠΈ 17Π -ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° Π½Π° ΡΡΠΎΠ²Π½ΠΈ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π»ΠΈΠ½ΠΈΠΉ ΡΠ°ΠΊΠ° Π³ΡΡΠ΄ΠΈ (Π»ΠΈΠ½ΠΈΡ MCF7) ΠΈ ΡΠ°ΠΊΠ° ΠΏΡΠΎΡΡΠ°ΡΡ (Π»ΠΈΠ½ΠΈΡ LNCaP).
4. ΠΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ l, 25(OH)2D3 ΠΈ 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° Π½Π° Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² ΠΠΠ -ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, ΠΏΠ΅ΡΠ΅Π΄Π°ΡΡΠ΅Π³ΠΎ ΡΠΈΠ³Π½Π°Π» ΠΎΡ ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠΈ ΠΊΠ»Π΅ΡΠΊΠΈ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌ ΡΡΡΡΠΊΡΡΡΠ°ΠΌ.
Π²ΡΠ²ΠΎΠ΄Ρ.
1. ΠΡΠΎΠ΄ΡΠΊΡΠΈΡ Π ΠΠ ΠΈ Π±Π΅Π»ΠΊΠ° KGF Π³Π΅Π½ΠΎΠΌ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° ΠΊΠ΅ΡΠ°ΡΠΈΠ½ΠΎΡΠΈΡΠΎΠ² kgf Π²ΠΎΠ·ΡΠ°ΡΡΠ°Π΅Ρ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½Π° D3 (l, 25(OH)2D3) ΠΈ 17(3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π°.
2. Π 5″ -ΡΠ»Π°Π½ΠΊΠΈΡΡΡΡΠ΅ΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ Π³Π΅Π½Π° kgf Π½Π°ΠΉΠ΄Π΅Π½Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ, ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎ ΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΡΠ΅ Π·Π° ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ Π³Π΅Π½Π° kgf ΡΡΠ΅ΡΠΎΠΈΠ΄Π½ΡΠΌΠΈ Π³ΠΎΡΠΌΠΎΠ½Π°ΠΌΠΈ ΠΈ Π²ΠΈΡΠ°ΠΌΠΈΠ½ΠΎΠΌ D3.
3. ΠΠ»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ (Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 1−6 ΡΡΡ) Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ l, 25(OH)2D3 ΠΈ 17)3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π° ΠΏΠΎ-ΡΠ°Π·Π½ΠΎΠΌΡ ΠΌΠ΅Π½ΡΠ΅Ρ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ MCF7 ΠΈ LNCaP. 17Π -ΡΡΡΡΠ°Π΄ΠΈΠΎΠ» Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅Ρ, a l, 25(OH)2D3 ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΠ΅Ρ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ MCF7 ΠΈ LNCaP.
4. ΠΡΡΡΡΡΠΌ ΠΎΡΠ²Π΅ΡΠΎΠΌ (Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΌΠΈΠ½ΡΡ) Π½Π° ΡΡΠΈΠΌΡΠ»ΡΡΠΈΡ l, 25(OH)2D3 ΡΠ²Π»ΡΠ΅ΡΡΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΠ -ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π° Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΎΠ±Π΅ΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ Π»ΠΈΠ½ΠΈΠΉ. ΠΠ»ΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΠΏΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠ° (Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΈΡ ΡΡΡΠΎΠΊ) 1,25-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ²ΠΈΡΠ°ΠΌΠΈΠ½ΠΎΠΌ D3 ΠΏΠΎΠ΄Π°Π²Π»ΡΠ΅Ρ Π±ΡΡΡΡΡΠΉ ΠΎΡΠ²Π΅Ρ ΠΊΠ»Π΅ΡΠΎΠΊ — ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΠΠ -ΠΊΠΈΠ½Π°Π· ΠΏΡΠΈ Π΄Π΅ΠΉΡΡΠ²ΠΈΠΈ 17{3-ΡΡΡΡΠ°Π΄ΠΈΠΎΠ»Π°.
Π‘ΠΏΠΈΡΠΎΠΊ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
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