Sun Zhulei, Huang Gui, Cheng Hepeng
Department of Pathology, Huaihe Hospital of Henan University, Kaifeng, People's Republic of China.
Department of Urology, Huaihe Hospital of Henan University, Kaifeng, People's Republic of China.
Cancer Manag Res. 2019 Jul 4;11:6079-6090. doi: 10.2147/CMAR.S200998. eCollection 2019.
() has been documented to be implicated in carcinogenesis and chemoresistance in solid tumors. Here, we explored the biological role and regulatory mechanism of in progression and chemoresistance of urothelial carcinoma of the bladder (UCB).
() () mRNA and expression was determined by quantitative reverse transcription polymerase chain reaction. Western blot was performed to determine the protein levels of Nrf2, p-glycoprotein (p-gp), Ki-67 (Ki67), matrix metalloproteinase (MMP)-2 and MMP-9 and cleaved caspase-3. The effects of either or knockdown on the proliferation, invasion, apoptosis and adriamycin (ADM) resistance of UCB cells were evaluated by CCK-8 assay, transwell invasion assay and flow cytometry analysis. Xenograft tumor assay was carried out to confirm the role of and in ADM resistance of UCB cells in vivo.
and were upregulated in UCB tissues and cell lines. A positive correlation between and expression was discovered in UCB tissues. Moreover, and expression levels were higher in ADM-resistant cells compared with those in parental cells. Furthermore, positively regulated the expression of in UCB cells. Knockdown of either or led to the inhibition of cell proliferation and invasion and promotion of cell apoptosis, accompanying with down-regulation of Ki67, MMP-2 and MMP-9 and up-regulation of cleaved caspase-3. Knockdown of either or enhanced the sensitivity of BIU-87/ADM and T24/ADM cells to ADM, as indicated by decreased expression of p-gp. Besides, knockdown of either or inhibited tumor growth in the absence or presence of ADM in vivo.
induces the up-regulation of to promote progression and ADM resistance in UCB.
()已被证明与实体瘤的致癌作用和化疗耐药性有关。在此,我们探讨了()在膀胱尿路上皮癌(UCB)进展和化疗耐药中的生物学作用及调控机制。
采用定量逆转录聚合酶链反应测定()()mRNA和()表达。进行蛋白质印迹法以测定Nrf2、P-糖蛋白(p-gp)、Ki-67(Ki67)、基质金属蛋白酶(MMP)-2和MMP-9以及裂解的半胱天冬酶-3的蛋白水平。通过CCK-8法、Transwell侵袭试验和流式细胞术分析评估()或()敲低对UCB细胞增殖、侵袭、凋亡和阿霉素(ADM)耐药性的影响。进行异种移植瘤试验以证实()和()在体内UCB细胞ADM耐药中的作用。
()和()在UCB组织和细胞系中上调。在UCB组织中发现()和()表达呈正相关。此外,与亲本细胞相比,ADM耐药细胞中()和()表达水平更高。此外,()在UCB细胞中正向调节()的表达。敲低()或()导致细胞增殖和侵袭受到抑制,细胞凋亡增加,同时Ki67、MMP-2和MMP-9下调,裂解的半胱天冬酶-3上调。敲低()或()增强了BIU-87/ADM和T24/ADM细胞对ADM的敏感性,表现为p-gp表达降低。此外,敲低()或()在体内无论有无ADM的情况下均抑制肿瘤生长。
()诱导()上调以促进UCB的进展和ADM耐药。