硼替佐米通过抑制前列腺癌细胞中的 Wnt/β-连环蛋白信号通路增强米托蒽醌的抗肿瘤活性。
Bortezomib potentiates antitumor activity of mitoxantrone through dampening Wnt/β-catenin signal pathway in prostate cancer cells.
机构信息
Institute of Precision Medicine, Jining Medical University, Jining, 272067, China.
Center for Experimental Medicine, School of Public Health, Jining Medical University, Jining, 272067, China.
出版信息
BMC Cancer. 2021 Oct 13;21(1):1101. doi: 10.1186/s12885-021-08841-1.
BACKGROUND
Bortezomib (BZM), alone or in combination with other chemotherapies, has displayed strong anticancer effects in several cancers. The efficacy of the combination of BZM and mitoxantrone (MTX) in treating prostate cancer remains unknown.
METHODS
Anticancer effects of combination of BZM and MTX were determined by apoptosis and proliferation assay in vivo and in vitro. Expression of β-Catenin and its target genes were characterized by western blot and Real-time PCR.
RESULTS
BZM significantly enhanced MTX-induced antiproliferation in vivo and in vitro. Mice administered a combination of BZM and MTX displayed attenuated tumor growth and prolonged survival. BZM significantly attenuated MTX-induced apoptosis. Moreover, the combination of BZM and MTX contributed to inhibition of the Wnt/β-Catenin signaling pathway compared to monotherapy.
CONCLUSIONS
This study demonstrates that BZM enhances MTX-induced anti-tumor effects by inhibiting the Wnt/β-Catenin signaling pathway in prostate cancer cells.
背景
硼替佐米（BZM）单独或与其他化疗药物联合使用在多种癌症中显示出强大的抗癌作用。BZM 与米托蒽醌（MTX）联合治疗前列腺癌的疗效尚不清楚。
方法
通过体内和体外的细胞凋亡和增殖实验来确定 BZM 和 MTX 联合的抗癌效果。通过 Western blot 和实时 PCR 来研究 β-连环蛋白及其靶基因的表达。
结果
BZM 显著增强了 MTX 在体内和体外诱导的增殖抑制作用。给予 BZM 和 MTX 联合治疗的小鼠显示出肿瘤生长减弱和存活时间延长。BZM 显著减弱了 MTX 诱导的细胞凋亡。此外，与单药治疗相比，BZM 和 MTX 的联合使用有助于抑制 Wnt/β-连环蛋白信号通路。
结论
本研究表明，BZM 通过抑制 Wnt/β-连环蛋白信号通路增强了 MTX 诱导的前列腺癌细胞的抗肿瘤作用。
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