Up-regulation of peroxiredoxin-1 promotes cell proliferation and metastasis and inhibits apoptosis in cervical cancer
Up-regulation of peroxiredoxin-1 promotes cell proliferation and metastasis and inhibits apoptosis in cervical cancer
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DOI：
10.7150/jca.37147
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Zhu, Xueqiong
中科院分区：
文献类型：
--
作者：
Lu, Ermei;Hu, Xiaoli;Zhu, Xueqiong
目的：为探讨过氧化物氧还蛋白1（peroxiredoxin 1，PRDX 1）对宫颈癌细胞生物学行为的影响及其可能机制，采用免疫组化方法检测PRDX 1在宫颈癌组织及癌旁组织中的表达。构建了含有PRDX 1-cDNA或针对PRDX 1的shRNA的慢病毒，以在SiHa宫颈癌细胞中过表达或敲减PRDX 1。CCK-8和BrdU掺入法检测细胞增殖，AnnexinV-PE /7AAD法检测细胞凋亡。划痕法和transwell侵袭实验检测PRDX 1过表达或抑制后的迁移和侵袭活性。结果：PRDX 1蛋白在裸鼠移植瘤组织中的表达明显高于癌旁正常组织，且与癌旁正常组织相比差异有统计学意义（P < 0. 05）。PRDX 1过表达与肿瘤分期、淋巴结转移和分化程度有关。PRDX 1过表达可通过增加Nanog、增殖细胞核抗原（PCNA）、B细胞淋巴瘤-2（Bcl-2）的表达，下调Bcl-2相关X蛋白（BAX）的表达，促进SiHa宫颈癌细胞的增殖，抑制其凋亡。PRDX 1过表达通过上调Snail和基质金属蛋白9（MMP-9）的表达，下调E-cadherin的表达，增强SiHa宫颈癌细胞的侵袭和迁移能力。PRDX 1的敲除导致相反的结果。结论：PRDX 1可能通过调控相关蛋白的表达，促进宫颈癌SiHa细胞的增殖、迁移和侵袭，抑制细胞凋亡。
Objective: To investigate the effect of peroxiredoxin 1 (PRDX1) on the biological behavior of cervical cancer cells and the possible mechanism.Materials and methods: The expression of PRDX1 in human cervical cancer tissues and adjacent non-tumor tissues were detected by immunohistochemistry (IHC). Lentivirus containing PRDX1-cDNA or shRNA against PRDX1 was constructed to overexpress or knockdown PRDX1 in SiHa cervical cancer cells. Cell proliferation was tested by CCK-8 and BrdU incorporation assay and cell apoptosis was evaluated by AnnexinV-PE /7AAD assay. Scratch wound and transwell invasion assay were used to test migration and invasion activity after PRDX1 overexpressed or suppressed. Furthermore, the effect of PRDX1 on cell proliferation and apoptosis was also studied using a xenograft model of nude mice.Results: The expression of PRDX1 protein was significantly up-regulated in the tumor tissues compared with the paired adjacent non-tumor tissues. Meanwhile, PRDX1 overexpression was associated with tumor stage, lymphatic metastasis and differentiation. Overexpression of PRDX1 significantly promoted proliferation and inhibited apoptosis by increasing the expression of Nanog, proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2) and downregulating the expression of Bcl2-associated X protein (BAX) in SiHa cervical cancer cells. Moreover, PRDX1 overexpression increased invasion and migration of SiHa cervical cancer cells via up-regulating the expression of Snail and matrix metalloprotein 9 (MMP-9) and down-regulating the expression of E-cadherin. Knockdown of PRDX1 resulted in the opposite results. The role of PRDX1 in promoting SiHa cervical cancer cell proliferation and inhibiting apoptosis has also been confirmed in vivo in a mouse xenograft model.Conclusions: PRDX1 promoted cell proliferation, migration, and invasion and suppressed apoptosis of cervical cancer possibly via regulating the expression of related protein.