Department of Obstetrics and Gynecology, the First People's Hospital of Jingzhou City, Jingzhou, Hubei Province, China.
Department of Women's Tumor, Jingzhou Cancer Hospital, Jingzhou, Hubei Province, China.
Braz J Med Biol Res. 2020 Feb 7;53(2):e8901. doi: 10.1590/1414-431X20198901. eCollection 2020.
The objective of this study was to explore the role of the SULF2-mediated ERK/AKT signaling pathway in cervical cancer. SULF2 expression was detected in tumor tissues and tumor-adjacent normal tissues from cervical cancer patients. HeLa cells were divided into six groups: control group, NC group, SULF2 siRNA group, SULF2 group, SULF2 + LY294002 group, and SULF2 + U0125 group. In each group, HeLa cells received the corresponding treatment, followed by measurement of the cellular biological characteristics and expression of the ERK/AKT signaling pathway. We also confirmed the effect of SULF2 in vivo using a xenograft model in nude mice. SULF2 was upregulated in cervical cancer tissues, which was specifically associated with the clinical stage, histological differentiation, and lymphatic metastasis. Compared to the control group, the SULF2 siRNA group displayed decreased expression of SULF2, concomitant with reduced proliferation, migration, and invasion, but there was an increase in the apoptosis rate of HeLa cells, as well as downregulation of the p-Akt/Akt, p-ERK/ERK, and Bax/Bcl-2 ratios and cyclin D1. Additionally, tumor growth was significantly inhibited in the xenograft model of nude mice. The results in the SULF2 group were quite the opposite in which SULF2 facilitated the growth of cervical cancer cells, which was reversed by LY294002 or U0126. SULF2 is highly expressed in cervical cancer, and thus, downregulation of SULF2 can inhibit the ERK1/2 and AKT signaling pathways to suppress the proliferation, invasion, and migration of cervical cancer cells while facilitating apoptosis.
本研究旨在探讨 SULF2 介导的 ERK/AKT 信号通路在宫颈癌中的作用。检测了宫颈癌患者肿瘤组织及癌旁正常组织中 SULF2 的表达。将 HeLa 细胞分为 6 组：对照组、NC 组、SULF2 siRNA 组、SULF2 组、SULF2+LY294002 组、SULF2+U0125 组。每组 HeLa 细胞接受相应处理后，检测细胞生物学特性及 ERK/AKT 信号通路的表达情况。还通过裸鼠异种移植模型证实了 SULF2 的作用。SULF2 在宫颈癌组织中上调，且与临床分期、组织学分化和淋巴转移密切相关。与对照组相比，SULF2 siRNA 组 SULF2 表达下调，同时 HeLa 细胞增殖、迁移和侵袭减少，而细胞凋亡率增加，p-Akt/Akt、p-ERK/ERK 和 Bax/Bcl-2 比值及 cyclin D1 降低。此外，裸鼠异种移植模型中肿瘤生长明显受到抑制。SULF2 组结果则相反，SULF2 促进了宫颈癌细胞的生长，而 LY294002 或 U0126 可逆转这一作用。SULF2 在宫颈癌中高表达，下调 SULF2 可抑制 ERK1/2 和 AKT 信号通路，抑制宫颈癌细胞的增殖、侵袭和迁移，促进凋亡。
