硼替佐米或联合三氧化二砷治疗HL-60白血病细胞移植瘤裸鼠的实验研究

Effect of bortezomib used alone or in combination with arsenic trioxide on HL-60 cell xenograft in nude mice

目的探讨硼替佐米(Bor)单独和联合三氧化二砷(As2O3)对HL-60白血病细胞移植瘤裸鼠的抗瘤作用、作用机制及药物毒性。方法建立皮下移植瘤裸鼠模型,随机分为4组,即生理盐水(NS)组、Bor单药组、As2O3单药组、Bor联合As2O3组,比较各组的抑瘤作用和裸鼠一般状态的变化,并对移植瘤进行细胞凋亡和免疫组化检测。结果Bor单独或联合As2O3均能抑制移植瘤生长和延长裸鼠生存时间,并诱导肿瘤细胞凋亡和抑制其增殖,其中以联合用药组效果最好,且未引起重要脏器损害。结论Bor联合As2O3对HL-60白血病细胞移植瘤裸鼠具有显著的抗瘤作用,此作用可能与诱导肿瘤细胞凋亡和抑制其增殖有关,且无明显毒副作用。

Objective To assess the antitumor efficacy and adverse effects of bortezomib either used alone or in combination with arsenic trioxide for transplanted tumor in nude mice.Methods Nude mice bearing HL-60 cell xenografts were randomized into 4 groups to receive treatment with normal saline,bortezomib,arsenic trioxide,bortezomib plus arsenic trioxide.The tumor growth inhibition and general condition of the nude mice were observed,and in situ TUNEL assay and immunohistochemistry were performed on the transplanted tumors.Results Bortezomib alone and in combination with arsenic trioxide could both inhibit the growth of the transplanted tumors,prolong the survival of the nude mice,and induce cell apoptosis and growth inhibition of the HL-60 cells in vivo,and the combined administration exhibited even better effects.The administration was well tolerated with causing manifest vital organ damages in the mice.Conclusions Bortezomib in combination with arsenic trioxide has significant antitumor effect in nude mice bearing HL-60 cell xenografts possibly by inducing HL-60 cell apoptosis and growth inhibition without produceing no significant adverse effects.