| Objective: Angiogenesis has a close correlation with malignant blood diseases. VEGF and COX-2 are important factors of angiogenesis, also are closely related with occurrence and development of malignant blood diseases. The correlation between VEGF and COX-2 expression levels and the effects of COX-2 inhibitor on VEGF and COX-2 protein expression levels in malignant Hematonosis were explored in this subject.Methods: The mRNA levels of VEGF and COX-2 were measured by RQ-PCR in 96 samples acquired from adult malignant hematonosis patients and 20 normal controls, The protein expression levels of VEGF and COX-2 were checked by flow cytometry(FCM).Results:1 The VEGF mRNA expression levels in different groupsThe VEGF expression levels in acute leukemia(AL) group: the VEGF mRNA expression level of AL patients was 0.67±0.23,which was higher than that of normal control group(0.12±0.21)(P<0.05). VEGF expression level of primary AML patients was 0.77±0.27,compared with normal control group(P<0.05). The expression levels in M2 , M4 and M5 subgroups were 0.68±0.16, 0.79±0.32 and 0.75±0.25, respectively. That in M3 subgroup was 0.76±0.21, in ALL group was 0.22±0.61, in relapsed AL patients was 0.71±0.25, compared with normal control group(P<0.05).The remission rate of 38 cases of untreated AL patients who were treated was 81.6%(31/38). According to the VEGF mRNA expression level 0.67±0.23, divide untreated AL patients into two groups. The remission rate of the untreated AL patients was 95.4%(21/22)whose VEGF mRNA expression level is below 0.67±0.23 and that was 43.7%(7/16)whose VEGF mRNA expression level is up 0.67±0.23, compared with the former group (P<0.05). According to the COX-2 mRNA expression level 0.72±0.61, divide untreated AL patients into two groups. The remission rate of the untreated AL patients was 92%(23/25)whose COX-2 mRNA expression level is below 0.72±0.61 and that was 41.7%(5/12)whose COX-2 mRNA expression level is up 0.72±0.61, compared with the former group (P<0.05). The remission rate of untreated AL patients was 26.3%(5/19)who co-expressed VEGF mRNA and COX-2 mRNA.The VEGF expression level in untreated multiple myeloma(MM) group was 0.84±0.11,in relapsed MM patients was 0.77±0.09, compared with normal control group(P<0.05).The VEGF expression level in high risk MDS:the VEGF expression level of high risk MDS patients was 0.49±0.54, compared with normal control group(P<0.05), compared with primary AL group(P>0.05).The VEGF mRNA expression levels in different phases'CML:the VEGF expression level of chronic phase's CML patients was 0.43±0.42,which has statistics difference (P<0.05) compared with normal controls. The VEGF expression level of blasts crisis phase's CML patients was 0.66±0.31, which has statistics difference (P<0.05) compared with normal controls.2 The COX-2 mRNA expression levels in different groupsThe COX-2 expression level in AL group: the COX-2 mRNA expression level of AL patients was 0.72±0.61,which was higher than that of normal controls (0.24±34.7)(P<0.05). COX-2 expression level of primary AML patients was 0.77±0.37,which has statistics difference(P<0.05) compared with normal controls. The expression levels in M4 and M5 subgroups were 0.80±0.22, 0.74±0.62 respectively. That in M2 and M3 subgroup were 0.72±0.45 and 0.79±0.32, in ALL group was 0.22±0.61, in relapsed AL patients was 0.68±0.41, compared with normal control group(P<0.05).The COX-2 expression level in untreated multiple mteloma(MM) was 0.67±0.72,which has statistics difference (P<0.05) compared with normal controls. The COX-2 expression level of relapsed MM patients was 0.45±0.32, which has statistics difference (P<0.05) compared with normal controls.The COX-2 expression level in high risk MDS:the COX-2 expression level of high risk MDS patients was 0.73±0.52,which has statistics difference (P<0.05) compared with normal controls.The COX-2 mRNA expression level in different phases'CML:the COX-2 expression level of chronic phase's CML patients was 0.55±0.57,which has statistics difference (P<0.05) compared with normal controls. The COX-2 expression level of blasts crisis phase's CML patients was 0.81±0.12, which has statistics difference (P<0.05) compared with normal controls.3 The correlations between VEGF and COX-2 mRNA in different groupsThere were 10 cases of M3 in the AL set, including 9 cases expressed VEGF, and 7 cases expressed COX-2, and in co-expression cases, between VEGF and COX-2 mRNA expression levels has a positive relation. There were 7 cases of M4, including 6 cases expressed VEGF, and 6 cases expressed COX-2, and in 6 co-expression cases , between VEGF and COX-2 mRNA expression levels has a positive relation. There were 5 cases of M5, including 5 cases expressed VEGF, and 5 cases expressed COX-2, and in 5 co-expression cases, between VEGF and COX-2 mRNA expression levels has a positive relation.In 8 cases of MM, 5 cases expressed VEGF, and 7 cases expressed COX-2, and in 3 co-expression cases, the VEGF mRNA expression level was not related to that of COX-2.In 8 cases of high risk MDS, 7 cases expressed VEGF, and 3 cases expressed COX-2, and in 3 co-expression cases, the VEGF mRNA expression level was not related to that of COX-2 .In 10 cases of chronic phase's CML, 9 cases expressed VEGF, and 5 cases expressed COX-2, and in 5 co-expression cases,the VEGF mRNA expression level has a positive relation to that of COX-2.4 The effects of COX-2 inhibitor III on the expression levels of VEGF and COX-2 in U937 cellsThe COX-2 expression rate in the blank set was 98.6±0.5%. After 6 hours treated with COX-2 inhibitor III, the COX-2 expression rate in 5umol/l group was 98.6±0.5%, in 10umol/l group was 81.5±7.13%, in 50umol/l group was 71.7±6.28%. The VEGF expression rate in the blank set was 99.2±0.5%, and that of 5umol/l group was 97.5±5.2%, 10umol/l group was 96.7±2.47%, 50umol/l group was 83.5±7.23%.After 12 hours treated with COX-2 inhibitor III, the COX-2 expression rate of 5umol/l group was 89.4±5.22%, and that of 10umol/l group was 74.7±2.55%, 50umol/l group was 67.8±5.32%. The VEGF expression rate in the blank set was 99.2±0.5%, and that of 5umol/l group was 92.4±4.51%, 10umol/l group was 80.2±3.82%, 50umol/l group was 66.7±1.91%.After 24 hours treated with COX-2 inhibitor III ,the COX-2 expression rate of 5umol/l group was 77.5±2.85%, and that of 10umol/l group was 58.4±7.25%, 50umol/l group was 43.5±2.38%. The VEGF expression rate in the blank set was 99.2±0.5%, and that of 5umol/l group was 90.2±6.87%, 10umol/l group was 72.9±5.81%, 50 u mol/l group was 54.32±2.09%.Conclusion:VEGF and COX-2 genes were expressed in all groups of malignant hematonosis,but the expression levels were different. Co-expression of VEGF and COX-2 genes in primary AL patients could lead to worse prognosis.The VEGF and COX-2 protein expression levels were down-regulated by COX-2 inhibitor III in U937 cells simutanously.This result shows that VEGF and COX-2 has corelations in angiogenesis of malignant hematonosis.
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