Problemy radiatsiinoi medytsyny ta radiobiolohii · 2019
INFLUENCE OF COMBINED ACTION OF X-RADIATION AND CYCLOOXYGENASE-2 - MELOXIVET INHIBITOR ON VEGF AND PGE-2 CONTENT IN BLOOD OF RAT-TUMOR CARRIERS.
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Mitryayeva N A, Grebinyk L V, Uzlenkova N E
Аннотация
OBJECTIVE: The objective of this work was to study the effect of the combined action of X-radiation and the cyclooxygenase-2 (COX-2) inhibitor on the level of vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE-2) in blood serum of rat-tumor carriers at irradiation in different doses.
MATERIALS AND METHODS: 20 tumor-bearing rats of the Wistar population weighing 160-180 g, with transplanted Guerin carcinoma, fractionated irradiation (5 Gy + 5 Gy) and (0.5 Gy + 0.5 Gy) of the tumor growth zone on the RUM- 17 was carried out, with an interval between sessions of 24 hours. The drug «Meloxivet» - a selective inhibitor of cyclooxygenase-2 was administered 24 hours before irradiation and 2 hours before the second exposure (0.2 mg per 1 kg body weight). Blood sampling was performed by the method of life-time decapitation after 24 hours after the last fraction of irradiation. The content of VEGF in blood serum was determined by the method of enzyme immunoas- say using standardResults. After fractionated irradiation in a total dose of 1 Gy (0.5 Gy + 0.5 Gy), the level of VEGF was increased by 1.5 times compared with intact control, and in animals that were irradiated in a total dose of 10 Gy (5 Gy + 5 Gy ), the VEGF level was reduced by 1.92 times. That is, there was a difference in the content of VEGF in blood serum of rat tumor carriers, depending on the dose of irradiation: in a total dose of 1 Gy - stimulation of angiogenesis, and in the total dose of 10 Gy - a significant slowdown in this process. In the case of combined exposure to radiation (10 Gy) and the COX-2 inhibitor, meloxivet, the potential decrease in VEGF levels was 3.49 times compared to con- trol and 1.8 times with isolated exposure. At the same time, the level of PGE-2 also decreased with respect to iso- lated exposure by 1.5 times, indicating COX-2 inhibition. With a combined low dose (1 Gy) irradiation and COX-2- meloxivet inhibitor, VEGF levels were reduced by 1.1 times compared to control and 1.7 times relative to isolated exposure. At the same time, the level of PGE-2 also decreased in comparison with isolated radiation in 1,1 times. The obtained results indicate the influence of the combined act of irradiation and meloxivet on the level of VEGF and PGE-2, which causes the antiangiogenic effect.Сonclusions. It has been shown that low doses of ionizing radiation (1 Gy) and high doses (10 Gy) have a different effect on VEGF expression, and thus on angiogenesis processes. The combined effect of ionizing radiation and the COX-2 inhibitor (meloxivet) affects the level of PGE-2, VEGF, ie, the slowing of angiogenesis. In the case of large doses of exposure, this effect is even more expressed.
MATERIALS AND METHODS: 20 tumor-bearing rats of the Wistar population weighing 160-180 g, with transplanted Guerin carcinoma, fractionated irradiation (5 Gy + 5 Gy) and (0.5 Gy + 0.5 Gy) of the tumor growth zone on the RUM- 17 was carried out, with an interval between sessions of 24 hours. The drug «Meloxivet» - a selective inhibitor of cyclooxygenase-2 was administered 24 hours before irradiation and 2 hours before the second exposure (0.2 mg per 1 kg body weight). Blood sampling was performed by the method of life-time decapitation after 24 hours after the last fraction of irradiation. The content of VEGF in blood serum was determined by the method of enzyme immunoas- say using standardResults. After fractionated irradiation in a total dose of 1 Gy (0.5 Gy + 0.5 Gy), the level of VEGF was increased by 1.5 times compared with intact control, and in animals that were irradiated in a total dose of 10 Gy (5 Gy + 5 Gy ), the VEGF level was reduced by 1.92 times. That is, there was a difference in the content of VEGF in blood serum of rat tumor carriers, depending on the dose of irradiation: in a total dose of 1 Gy - stimulation of angiogenesis, and in the total dose of 10 Gy - a significant slowdown in this process. In the case of combined exposure to radiation (10 Gy) and the COX-2 inhibitor, meloxivet, the potential decrease in VEGF levels was 3.49 times compared to con- trol and 1.8 times with isolated exposure. At the same time, the level of PGE-2 also decreased with respect to iso- lated exposure by 1.5 times, indicating COX-2 inhibition. With a combined low dose (1 Gy) irradiation and COX-2- meloxivet inhibitor, VEGF levels were reduced by 1.1 times compared to control and 1.7 times relative to isolated exposure. At the same time, the level of PGE-2 also decreased in comparison with isolated radiation in 1,1 times. The obtained results indicate the influence of the combined act of irradiation and meloxivet on the level of VEGF and PGE-2, which causes the antiangiogenic effect.Сonclusions. It has been shown that low doses of ionizing radiation (1 Gy) and high doses (10 Gy) have a different effect on VEGF expression, and thus on angiogenesis processes. The combined effect of ionizing radiation and the COX-2 inhibitor (meloxivet) affects the level of PGE-2, VEGF, ie, the slowing of angiogenesis. In the case of large doses of exposure, this effect is even more expressed.