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目的探讨溴结构域及外端结构域(BET)抑制剂JQ1联合组蛋白去乙酰化酶抑制剂伏立诺他(SAHA)抗骨肉瘤的作用及相关分子机制。方法 JQ1单用、SAHA单用及JQ1联合SAHA分别处理骨肉瘤细胞SJSA1和MNNG/HOS后,利用MTT法结合药物协同指数(CI)检测药物对细胞的生长抑制作用并评定协同效果,克隆形成检测生长抑制作用,流式细胞仪检测细胞凋亡,Western blot法检测相关蛋白表达水平的改变。结果 JQ1联合SAHA协同抑制骨肉瘤细胞系SJSA1和MNNG/HOS生长,克隆形成及流式细胞仪检测证明JQ1联合SAHA能够协同抑制骨肉瘤生长并促进其凋亡,并明显上调Bax、下调Bcl-2蛋白的表达。结论 JQ1联合SAHA能够协同抑制骨肉瘤细胞生长、诱导其凋亡,其中Bax/Bcl-2可能是重要的靶点。
Objective To investigate the effect and related molecular mechanism of bromodomain and BET endostatin (JQ1) combined with vinorelbine (SAHA) on osteosarcoma. Methods After treatment of SJSA1 and MNNG / HOS in osteosarcoma cells with JQ1 alone, SAHA alone and JQ1 combined with SAHA, the growth inhibitory effect of the drugs on the cells was evaluated by MTT assay and drug synergy index (CI), and the synergistic effect was evaluated. Clone formation assay Growth inhibition, flow cytometry detection of apoptosis, Western blot detection of related protein expression levels change. Results JQ1 combined with SAHA inhibited the growth of osteosarcoma cell lines SJSA1 and MNNG / HOS. Clone formation and flow cytometry showed that JQ1 combined with SAHA could synergistically inhibit the growth and promote the apoptosis of osteosarcoma, and significantly upregulate Bax and Bcl-2 Protein expression. Conclusion JQ1 combined with SAHA can synergistically inhibit the growth of osteosarcoma cells and induce their apoptosis. Bax / Bcl-2 may be an important target.