全反式维甲酸和亚硒酸钠对HL-60细胞VEGF及其受体表达的影响

The Effect of All-Trans Retinoid Acid and Sodium Selenite(Na_2SeO_3) on VEGF and Its Receptor Expression in HL-60 Cells

为了探讨非骨髓毒性药物全反式维甲酸 (ATRA)及具有防癌作用的微量元素硒的化合物———亚硒酸钠(Na2 SeO3 )对HL 6 0细胞系血管内皮细胞生长因子 (VEGF)及其受体表达的影响 ,应用ELISA法检测药物作用前后细胞培养上清液中VEGF含量 ,流式细胞术测定细胞表面VEGF受体表达。结果发现 ,5 μmol/L和 10 μmol/L的ATRA作用 4 8小时和 72小时后细胞上清液中VEGF含量显著减低 ,ATRA在 4 8小时对HL 6 0细胞表面的VEGF受体表达无抑制作用 ,在 72小时可抑制细胞表面的受体表达。Na2 SeO3 在 5 μmol/L和 10 μmol/L浓度条件下作用 4 8小时、72小时 ,对HL 6 0细胞培养上清液中VEGF的含量无明显抑制效应 ,对HL 6 0细胞表面VEGF R的表达有显著的抑制作用。结论 :ATRA具有抑制白血病细胞HL 6 0VEGF及其受体表达的作用 ,Na2 SeO3 对HL 6 0细胞分泌VEGF无抑制作用 ,但可抑制HL 6 0细胞表面表达VEGF受体 ,其机制尚需进一步明确。由于ATRA和Na2 SeO3 无明显的骨髓抑制作用 ,但具有抗血管新生的活性 ,故推测它们与常规放化疗相结合 ,将会增强放化疗的疗效 ,减少后者的用量 ,降低毒性 ,有助于白血病的治疗。

In order to investigate the effect of non medullar toxicity drug -- all trans retinoid acid (ATRA) and cancer preventive trace element selenium compound -- sodium selenite (Na 2SeO 3) on the expression of vascular endothelial growth factor (VEGF) and its receptor in HL 60 cells, the expression of VEGF and its receptor in HL 60 cells were detected by ELISA technique and flow cytometry before and after treatment with two drugs. The results showed that the mean VEGF concentrations in the cultural supernatant of 5 and 10 μmol/L ATRA treated HL 60 cells for 48 and 72 hours were lower than those of the control group without adding ATRA. The differences between the ATRA treated groups and the control group were statistically significant (P=0.001, P=0.000, p<0.01, respectively). The levels of VEGF R on the surface of HL 60 cells also decreased after treatment with ATRA of 5 and 10 μmol/L for 72 hours, but at 48 hours the expression rates of VEGF R on HL 60 cells of the two ATRA treated groups were not significantly decreased. At 48 and 72 hours, Na 2SeO 3 of 5 and 10 μmol/L had no obvious effect on HL 60 secreting VEGF, but notablely inhibited the expression of VEGF R. In conclusion, ATRA could inhibit the expression of VEGF and its receptor in HL 60 cell. Na 2SeO 3 could not inhibit the expression of VEGF in HL 60 cell, but could decrease the receptor expression of VEGF, which mechanism should be further studied. ATRA and Na 2SeO 3 had not obvious medullar inhibition, but anti angiogenesis activity. It is suggested that combination of two drugs with conventional therapy may enhance the effect of radiotherapy and chemotherapy, and reduce the dose and thus toxicity of chemotherapeutic agents.