The Content of Vegf, Cox-2 and Pge-2 Depending on the Objective Response to Radiation Therapy in Combination With a Cox-2 Inhibitor in Patients With Non-Small Cell Lung Cancer

Abstract

Objective: to evaluate the levels of VEGF, COX-2, PGE-2 in comparison with the effectiveness of radiation therapy with or without a COX-2 inhibitor.
 Materials and methods. The study involved 38 patients with non-small cell lung cancer (NSCLC) aged 32 to 80 years (median — 66 years), stage III of the process (50 %) prevailed, histological studies revealed squamous cell cancer in 74 %. To evaluate the results of the study, patients were divided into 2 subgroups: 1 — a subgroup (20 patients who received radiation therapy (RT) in combination with a COX-2 inhibitor — ranselex), 2 — a subgroup (18 patients who received RT). Radiation therapy was performed on linear accelerators Clinac 600C. During RT, patients received a COX-2 inhibitor — ranselex 100 mg per day. To determine the content of angiogenesis factors VEGF, COX-2, and PGE-2, blood sampling was performed in patients before irradiation and after a course of radiotherapy. The content of VEGF, COX-2, and PGE-2 was determined in blood serum by ELISA using standard reagent kits: of Vector-Best CJSC (Russia) for VEGF, commercial reagent kits of Invitrogen COX-2 ELISA Kit (Great Britain) and Prostaglandin T2 ELISA Kit (Germany).
 Results. An elevated level of VEGF, COX-2, PGE-2 in the blood serum of patients with NSCLC before radiation treatment was revealed, which indicates the activity of neoangiogenesis processes in the tumor. It was found that in patients with NSCLC after RT in combination with the COX-2 inhibitor ranselex, a 1.9-fold decrease in VEGF was observed against a 2.4-fold decrease in the COX-2 content and 1.7-fold PGE-2. In RT without ranselex, VEGF decreased by 1.4 times and the levels of COX-2 and PGE-2 did not change, which indicates inhibition of the COX-2 inhibitor of angiogenesis. The relationship between the concentration of the pro-angiogenic factor VEGF and the levels of COX-2, PGE-2 and the objective response with which the direct effect of RT was evaluated was established. With regression of the tumor process, a decrease in the level of VEGF was observed, more pronounced in RT with ranselex, which indicates the effectiveness of RT. With progression, a consistently high level of VEGF was observed, which is an unfavorable sign and is possibly associated with the tumor resistance to the therapy and the further unfavorable course of the disease.
 Conclusions. The relationship between the concentration of pro-angiogenic factors — VEGF, COX-2, PGE-2 and the objective response was determined, for which the direct effect of radiation therapy with or without a COX-2 inhibitor of ranselex (regression, stabilization, progression) was evaluated. It was shown that a more pronounced decrease in VEGF content is observed after radiation therapy (RT) with ranselex compared with RT without ranselex, which indicates inhibition of COX-2 inhibitor angiogenesis, and thereby leads to an increase in the effectiveness of RT.