Bevacizumab synergises with the BCL 2 inhibitor venetoclax to effectively treat B-cell non-Hodgkin's lymphoma (Retracted article. See vol. 109, pg. 118, 2022)
Bevacizumab synergises with the BCL 2 inhibitor venetoclax to effectively treat B-cell non-Hodgkin's lymphoma (Retracted article. See vol. 109, pg. 118, 2022)
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贝伐珠单抗与 BCL 2 抑制剂 Venetoclax 协同作用，可有效治疗 B 细胞非霍奇金淋巴瘤
DOI：
10.1111/ejh.13279
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发表时间：
2019-07-03
影响因子：
3.1
通讯作者：
Liu, Xiaoxia
中科院分区：
文献类型：
--
作者：
Wang, Li;Peng, Shaoyong;Liu, Xiaoxia
目的我们的研究表明VEGF-A介导的自分泌信号在促进SU-DHL-6细胞的存活和增殖中具有潜在的作用，但细胞在贝伐单抗处理后不能发生凋亡，而是减少增殖。因此，我们想进一步研究维奈托克（BCL 2抑制剂）与贝伐单抗联合治疗B细胞NHL的抗肿瘤疗效。方法采用人源性细胞因子抗体芯片、RT-qPCR、Western blot、ELISA、细胞凋亡检测及异种移植小鼠模型等方法。结果SU-DHL-6细胞具有细胞密度依赖性的存活和生长。利用人源性细胞因子抗体芯片检测SU-DHL-6细胞中VEGF-A的表达，结果显示VEGF-A的表达与细胞密度呈正相关，提示VEGF-A在SU-DHL-6细胞的存活和增殖中起重要作用。此外，异种移植的SU-DHL-6细胞在小鼠中形成肿瘤，这些肿瘤响应于VEGF刺激而生长。GEO数据集也提示VEGF-A高表达反映预后不良。贝伐珠单抗和navitoclax的联合治疗在体外可显著诱导细胞死亡，并降低肿瘤大小和重量，在体内耐受性良好。结论我们的研究结果提出了一种新的联合策略，其中贝伐单抗与BCL 2抑制剂venetoclax协同作用，对B细胞NHL有效。
Objectives Our present study has shown a potential role for VEGF-A-mediated autocrine signalling to promote survival and proliferation of SU-DHL-6 cells, but the cells could not undergo apoptosis but rather decrease proliferation after bevacizumab treatment. Therefore, we would like to further study the antitumour efficacy of venetoclax (BCL2 inhibitor) in combination with bevacizumab in B-cell NHL. Methods The human cytokine antibody array, RT-qPCR, Western blot, ELISA, apoptosis assay and xenografted mouse model et al were used. Results We described a unique phenomenon that SU-DHL-6 cells showed cell density-dependent survival and growth. Then, we suggested the expression of VEGF-A was positively correlated with the cell density using a human cytokine antibody array and indicated an important role of VEGF-A in the survival and proliferation of SU-DHL-6 cells. Additionally, xenografted SU-DHL-6 cells formed tumours in mice that grew in response to VEGF stimulation. GEO data set also suggested that high VEGF-A expression reflected poor prognosis. The combination therapy with bevacizumab and navitoclax could significantly induce of cell death in vitro and reduce the tumour size and weight with well tolerated in vivo. Conclusions Our findings propose a novel combined strategy in which bevacizumab synergises with the BCL2 inhibitor venetoclax that is effective against B-cell NHL.