The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by flow cytometry and western blotting, respectively. Immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time- and dose-dependent manner. SiHa cells were treated with 1 or 5 µM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 significantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This finding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.

本研究的目的是研究选择性 I 类组蛋白脱乙酰酶抑制剂 (HDACi) 4SC-202 是否通过靶向催乳素受体 (PRLR) 在宫颈癌 (CC) 中发挥抗肿瘤作用。CCK-8 和集落形成测定用于评估 4SC-202 对体外 CC 细胞增殖的影响。4SC-202 对 SiHa 细胞的细胞周期分布和细胞凋亡的影响分别通过流式细胞术和蛋白质印迹法测定。进行免疫荧光、蛋白质印迹和定量实时聚合酶链反应 (qRT-PCR) 以检测 CC 细胞中 PRLR 相关通路的活性和 PRLR 表达。建立裸鼠异种移植瘤模型，检测4SC-202对体内肿瘤生长、凋亡及PRLR相关通路的影响。采用生化分析仪和H&E染色检测血清生化指标和器官毒性。4SC-202 在体外以时间和剂量依赖性方式抑制 CC 细胞（SiHa、HeLa 和 CaSki）的增殖。SiHa 细胞用 1 或 5 µM 4SC-202 处理 72 小时，然后进行各种功能测定。测定显示，4SC-202 显着诱导 G2/M 期阻滞和细胞凋亡，同时抑制 PRLR 相关通路的活性和 PRLR 表达。此外，4SC-202 在体内减少肿瘤生长并诱导细胞凋亡。4SC-202在小鼠模型中下调PRLR的表达及PRLR相关通路的活性，对血清生化指标无影响，对小鼠器官无毒性。这一发现表明 4SC-202 可作为 CC 的新型治疗剂。