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首页> 外文期刊>Cellular Physiology and Biochemistry >Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma
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Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma

机译：抑制BRD4抑制肾癌细胞的细胞增殖并诱导其凋亡。

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>Background/Aims: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. Methods: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. Results: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. Conclusions: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.
机译：> 背景/目标： 肾细胞癌（RCC）仍然是顽固的泌尿生殖系统恶性肿瘤。 RCC对化学疗法或靶向疗法的耐药性可能是由于复杂的潜在分子机制和不足的理解。这项研究的目的是评估bromodomain-4蛋白（BRD4）在RCC中的表达和作用，并评估BRD4抑制剂JQ1在RCC治疗中的作用。 方法 ： 通过qRT-PCR和Western blot检测RCC组织和细胞中BRD4的表达水平。通过MTT测定和流式细胞术评估BRD4敲低或JQ1对RCC细胞的作用。通过异种移植实验评估了体内处理的效果。 结果： BRD4在RCC中明显过量表达，与肿瘤分期和淋巴结转移有关。抑制BRD4可抑制RCC细胞增殖，在体外诱导细胞凋亡，并在体内抑制肿瘤生长。抑制BRD4降低BCL2和C-MYC表达，同时增加BAX和切割caspase3表达，并显着减少BRD4向BCL2启动子的募集。 结论： 我们的研究表明BRD4可能在RCC进展中起关键作用，并且是针对这种顽固性疾病的药物治疗的新的有希望的靶标。

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