3 research outputs found
Enhancing effect of new biological response modifier sulfoethylated (1β3)-Ξ²-D-glucan on antitumor activity of cyclophosphamide in the treatment
Aim: One of the advanced methodologies of the tumor therapy is the application of the so-called biological response modifiers used for activation of the endogenous antitumor mechanisms and combined with classical cytotoxic agents. The aim of this work was the investigation of the effect of sulfoethylated (1β3)-Ξ²-D-glucan (SEG) in the treatment of experimental murine leukoses in combination with cyclophosphamide (CPA) and its ability to modulate the activity of lysosomal enzymes in tumor tissues. Materials and Methods: The solid forms of inoculated murine leukoses P388 and L1210/1 were transplantated to male DBA/2 mice. The therapy was performed by treating animals with CPA (Biokhimik, Saransk, Russia) alone or in combination with SEG (Institute of Chemistry, Slovak Academy of Sciences, Slovakia). CPA was administered in saline as a single intraperitoneal (ip) injection on the 10th day after tumor transplantation; SEG was administered to mice ip 3 days after tumor transplantation with the intervals in 3 days. The therapy effect was estimated by measuring of solid tumor volume. Activity of the cysteine proteases β cathepsins B and L β was measured fluorometrically using fluorescent substrates Z-Arg-Arg-MCA and Z-Phe-Arg-MCA (Sigma, USA), respectively. The apoptosis was estimated evaluating the number of cells with fragmented nuclei using optical microscope. Results: It has been demonstrated that application SEG leads to inhibition of tumor growth and potentiates therapeutic action of CPA, especially at repeated administrations during the whole treatment/observation At addition of SEG, therapeutic effect of a one-half reduced dose of CPA is equal or higher than that of the full dose. Therapeutic action of CPA and SEG on the studied tumors is realized predominantly through induction of apoptosis and is accompanied by a substantial increase of the activity of cysteine proteases cathepsins B and L in tumor tissues. The highest cathepsin B and cathepsin L activity in tumor tissue accompanied with the strongest inhibition of tumor growth. It is suggested that this phenomenon is due to the infiltration of the macrophages rich in the named enzymes into the tumor, where they phagocytize the apoptotic cells and tissue debris. Conclusion: Utilization of this polysaccharide BRM, sulfoethylated (1β3)-Ξ²-D-glucan, might potentially enhance efficiency of antitumor therapy with standard cytostatics without a need of substantial increase of their dosage and hence avoiding their toxic side-effects.Π¦Π΅Π»Ρ: ΠΎΠ΄Π½ΠΈΠΌ ΠΈΠ· ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ°ΠΊ Π½Π°Π·ΡΠ²Π°Π΅ΠΌΡΡ
ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΎΡΠΎΠ²
Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ°, ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΠΌΡΡ
Π΄Π»Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΠΈ ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡΡΠ΅ΠΌΡΡ
Ρ
ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌΠΈ. Π¦Π΅Π»Ρ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ β ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠ° ΡΡΠ»ΡΡΠΎΡΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ (1β
3)-Ξ²-D-Π³Π»ΠΈΠΊΠ°Π½Π° (SEG) ΠΏΡΠΈ Π»Π΅ΡΠ΅Π½ΠΈΠΈ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ
Π»Π΅ΠΉΠΊΠΎΠ·ΠΎΠ² ΠΌΡΡΠ΅ΠΉ Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΡΠΈΠΊΠ»ΠΎΡΠΎΡΡΠ°Π½ΠΎΠΌ (Π‘Π Π) ΠΈ Π΅Π³ΠΎ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ
ΠΌΠΎΠ΄ΡΠ»ΠΈΡΠΎΠ²Π°ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π»ΠΈΠ·ΠΎΡΠΎΠΌΠ½ΡΡ
ΡΠ΅ΡΠΌΠ΅Π½ΡΠΎΠ² Π² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ: ΡΠΎΠ»ΠΈΠ΄Π½ΡΠ΅ ΡΠΎΡΠΌΡ ΠΏΠ΅ΡΠ΅Π²ΠΈΠ²Π°Π΅ΠΌΡΡ
Π»Π΅ΠΉΠΊΠΎΠ·ΠΎΠ² ΠΌΡΡΠ΅ΠΉ Π 388 ΠΈ L1210/1 ΡΡΠ°Π½ΡΠΏΠ»Π°Π½ΡΠΈΡΠΎΠ²Π°Π»ΠΈ ΠΌΡΡΠ°ΠΌ-ΡΠ°ΠΌΡΠ°ΠΌ DBA/2. ΠΠ»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΠΈ Π‘Π Π (ΠΠΈΠΎΡ
ΠΈΠΌΠΈΠΊ,
Π‘Π°ΡΠ°Π½ΡΠΊ, Π ΠΎΡΡΠΈΡ) ΠΈ Π΅Π³ΠΎ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΡ Ρ SEG (ΠΠ½ΡΡΠΈΡΡΡ Ρ
ΠΈΠΌΠΈΠΈ Π‘Π»ΠΎΠ²Π°ΡΠΊΠΎΠΉ ΠΠΊΠ°Π΄Π΅ΠΌΠΈΠΈ ΠΠ°ΡΠΊ, ΠΡΠ°ΡΠΈΡΠ»Π°Π²Π°, Π‘Π»ΠΎΠ²Π°ΠΊΠΈΡ). Π‘Π Π Π²Π²ΠΎΠ΄ΠΈΠ»ΠΈ
Π²Π½ΡΡΡΠΈΠ±ΡΡΡΠΈΠ½Π½ΠΎ Π½Π° 10 ΡΡΡ ΠΏΠΎΡΠ»Π΅ ΠΏΠ΅ΡΠ΅Π²ΠΈΠ²ΠΊΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ; SEG Π²Π²ΠΎΠ΄ΠΈΠ»ΠΈ Π²Π½ΡΡΡΠΈΠ±ΡΡΡΠΈΠ½Π½ΠΎ Π½Π°ΡΠΈΠ½Π°Ρ Ρ 3 ΡΡΡ ΠΏΠΎΡΠ»Π΅ ΡΡΠ°Π½ΡΠΏΠ»Π°Π½ΡΠ°ΡΠΈΠΈ
Π»Π΅ΠΉΠΊΠΎΠ·ΠΎΠ² Ρ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»ΠΎΠΌ Π² 3 Π΄Π½Ρ. Π’Π΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΡΠ΅ΠΊΡ ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈ ΠΏΡΡΠ΅ΠΌ ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΠΎΠ±ΡΠ΅ΠΌΠ° ΡΠΎΠ»ΠΈΠ΄Π½ΠΎΠΉ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ. ΠΠΊΡΠΈΠ²Π½ΠΎΡΡΡ
ΡΠΈΡΡΠ΅ΠΈΠ½ΠΎΠ²ΡΡ
ΠΏΡΠΎΡΠ΅Π°Π· β ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½ΠΎΠ² Π ΠΈ L β ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ»ΠΈ ΡΠ»ΡΠΎΡΠΈΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡ ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΡΠ΅ ΡΡΠ±ΡΡΡΠ°ΡΡ
Z-Arg-Arg-MCA ΠΈ Z-Phe-Arg-MCA (Sigma, Π‘Π¨Π). ΠΠΏΠΎΠΏΡΠΎΠ· ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈ ΠΏΠΎ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ°ΠΌ ΠΏΠΎΠ΄ΡΡΠ΅ΡΠ° ΠΊΠ»Π΅ΡΠΎΠΊ Ρ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌΠΈ
ΡΠ΄ΡΠ°ΠΌΠΈ Π² ΡΠ²Π΅ΡΠΎΠ²ΠΎΠΌ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠ΅. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ: Π² ΡΠ°Π±ΠΎΡΠ΅ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ SEG ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΡΠΎΡΠΌΠΎΠΆΠ΅Π½ΠΈΡ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ
ΡΠΎΡΡΠ° ΠΈ ΠΏΠΎΡΠ΅Π½ΡΠΈΡΡΠ΅Ρ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΡΠ΅ΠΊΡ Π‘Π Π, ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎ ΠΏΡΠΈ ΠΏΠΎΠ²ΡΠΎΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ Π²ΡΠ΅Π³ΠΎ Π»Π΅ΡΠ΅Π½ΠΈΡ. Π ΡΠΎΡΠ΅ΡΠ°Π½ΠΈΠΈ Ρ SEG
ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΡΠ΅ΠΊΡ ΠΏΠΎΠ»ΠΎΠ²ΠΈΠ½Π½ΠΎΠΉ Π΄ΠΎΠ·Ρ Π‘Π Π ΡΠ°Π²Π½ΠΎΠ·Π½Π°ΡΠ΅Π½ ΠΈΠ»ΠΈ ΠΏΡΠ΅Π²ΡΡΠ°Π΅Ρ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΏΠΎΠ»Π½ΠΎΠΉ Π΄ΠΎΠ·Ρ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠ°. ΠΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅
Π‘Π Π ΠΈ SEG Π½Π° ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Π½ΡΠ΅ Π² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ ΡΠ΅Π°Π»ΠΈΠ·ΡΠ΅ΡΡΡ Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ ΡΠ΅ΡΠ΅Π· ΠΈΠ½Π΄ΡΠΊΡΠΈΡ Π°ΠΏΠΎΠΏΡΠΎΠ·Π° ΠΈ ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°Π΅ΡΡΡ
ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΌ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ΠΌ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠΈΡΡΠ΅ΠΈΠ½ΠΎΠ²ΡΡ
ΠΏΡΠΎΡΠ΅Π°Π· ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½ΠΎΠ² Π ΠΈ L Π² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ. ΠΠ°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠ°Ρ
Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½ΠΎΠ² Π ΠΈ L ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°Π΅ΡΡΡ ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΡΠΌ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΡΠΎΡΡΠ°. ΠΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎ ΡΡΠΎ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ΠΎ
ΠΈΠ½ΡΠΈΠ»ΡΡΡΠ°ΡΠΈΠ΅ΠΉ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ ΠΌΠ°ΠΊΡΠΎΡΠ°Π³Π°ΠΌΠΈ Ρ Π²ΡΡΠΎΠΊΠΈΠΌ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ΠΌ Π²ΡΡΠ΅Π½Π°Π·Π²Π°Π½Π½ΡΡ
ΡΠ΅ΡΠΌΠ΅Π½ΡΠΎΠ², Π³Π΄Π΅ ΠΎΠ½ΠΈ ΡΠ°Π³ΠΎΡΠΈΡΠΈΡΡΡΡ
ΠΊΠ»Π΅ΡΠΊΠΈ Π² Π°ΠΏΠΎΠΏΡΠΎΠ·Π΅. ΠΡΠ²ΠΎΠ΄Ρ: ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠ»ΡΡΠΎΡΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ (1β3)-Ξ²-D-Π³Π»ΠΈΠΊΠ°Π½Π°, Π½ΠΎΠ²ΠΎΠ³ΠΎ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΎΡΠ° Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ
ΠΎΡΠ²Π΅ΡΠ° Π΄Π°Π΅Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΠΏΠΎΠ²ΡΡΠΈΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΠΌΠΈ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠ°ΠΌΠΈ Π±Π΅Π·
ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΠΈΡ
Π΄ΠΎΠ·Ρ, ΡΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΈΠ·Π±Π΅ΠΆΠ°ΡΡ ΠΏΠΎΠ±ΠΎΡΠ½ΡΡ
ΡΡΡΠ΅ΠΊΡΠΎΠ² Π΄Π°Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ²