Abstract:

Abstract:Objective To observe the effects of oleanolic acid (OA) on apoptosis and the expression of Bcl-2 protein in HL-60 cells of the human leukemia implant model mice and investigate the therapeutic effect mechanism of OA on the human leukemia implant model mice. Methods 16 SCID mice were injected with 0.5 mL HL-60 cells(2×10⁷mL-1,cultivated in vitro),then the human promyelocytic leukemia implant models of mice were estabished.The model mice were divided into model group and treatment group(the mice were treated by subcutaneous injection with  200 mg.kg^-1 OA;at the same time,8 normal SCID mice were used as control group.2 weeks after treatment,the general condition and WBC classification in peripheral blood and bone marrow were observed.The invasive depth of HL-60 cells in spleen was tested by histopathologic examination;the apoptotic rate of HL-60 cells in spleen invasive leukemic was measured by TUNEL;the expression of  apoptosis related gene Bcl-2 was also detected by immunohistochemistry. Results The HL-60 cell implant models of SCID mice were established successfully;the bodyweight of the mice in treatment group(15.0 g±0.8 g) was obviously higher than that in control group(13.9 g±0.9　g) (P<0.01).The survival time of the mice in treatment group(50.3 d±5.5 d) was much longer than that in control group(37.1 d±4.4 d)(P<0.01).Compared with model group,the HL-60 cells in peripheral blood in treatment group trended to differentiate into normal WBC(P<0.05),the number of erythroid cells was reduced in bone marrow(P<0.05),the invasion of HL-60 cells in spleen was notably reduced(P<0.05),the apoptotic rate of HL-60 cells was increased(P<0.01) and the expression of Bcl-2 was decreased(P<0.01). Conclusion The HL-60 cell implant models of SCID mice are established successfully;OA could improve the general condition and increase the survival time of the leukemia implant model mice.OA could induce the apoptosis of HL-60 cells through down-regulation of Bcl-2 expression.