Chen Ziqin, Xiao Zemin, Tian Wei, Li Zongjuan, Wu Tao
Department of Oncology, First People's Hospital of Changde City, Changde 415003, Hunan, China.
Iran J Public Health. 2023 Jul;52(7):1476-1486. doi: 10.18502/ijph.v52i7.13249.
The drug resistance of chemotherapeutic agents leads to unsatisfactory survival rates for cervical cancer (CC) patients. We aimed to explore the effect of FOXP2 on the sensitivity of CC cells to cisplatin (DDP) and its mechanism in Changde, China in 2018.
A Total of 6 cervical cancer tissue samples including 3 patients with cisplatin sensitivity and 3 patients with cisplatin resistance, who received DDP-based treatment, were obtained from Changde First People's Hospital, Changde City during 2021, and FOXP2 level was detected by Western blot. The expression levels of FOXP2 and c-MET (hepatocyte growth factor receptor, c-MET) in cells were determined by q-PCR and Western blot analysis. The cell survival, apoptosis, and clone formation were analyzed by flow cytometry, MTT assay, or clone formation assay. Dual-luciferase reporter assays and Chromatin immunoprecipitation were applied to verify the regulation between FOXP2 and c-MET.
FOXP2 was downregulated in cisplatin-resistant cervical cancer tissues and cells compared with control. FOXP2 overexpression in SiHa/DDP cells inhibited cell proliferation and promoted cell apoptosis, whereas down-regulation of FOXP2 in SiHa cells had the opposite result. FOXP2 enhanced chemosensitive to DDP in CC cells. FOXP2 is negatively correlated with c-MET expression level in SiHa and SiHa/DDP cells. Mechanistically, FOXP2 binds to the promoter region of c-MET to regulate its expression in CC cells negatively. Overexpression of c-MET can attenuate the enhancement of DDP-induced apoptosis caused by FOXP2 overexpression.
This is a novel study on the role of FOXP2 in promoting the DDP sensitivity of CC cells by inhibiting c-MET. The FOXP2/c-MET signaling axis uncovered in the present study may be a novel therapeutic target for the DDP therapy resistance of CC.
化疗药物的耐药性导致宫颈癌（CC）患者的生存率不尽人意。2018年，我们旨在探讨FOXP2对CC细胞顺铂（DDP）敏感性的影响及其机制。
2021年期间，从常德市常德市第一人民医院获取了6份宫颈癌组织样本，其中包括3例顺铂敏感患者和3例顺铂耐药患者，这些患者均接受了基于DDP的治疗，并通过蛋白质免疫印迹法检测FOXP2水平。通过q-PCR和蛋白质免疫印迹分析确定细胞中FOXP2和c-MET（肝细胞生长因子受体，c-MET）的表达水平。通过流式细胞术、MTT法或克隆形成试验分析细胞存活、凋亡和克隆形成情况。应用双荧光素酶报告基因试验和染色质免疫沉淀法验证FOXP2与c-MET之间的调控关系。
与对照组相比，顺铂耐药的宫颈癌组织和细胞中FOXP2表达下调。SiHa/DDP细胞中FOXP2过表达抑制细胞增殖并促进细胞凋亡，而SiHa细胞中FOXP2下调则产生相反的结果。FOXP2增强了CC细胞对DDP的化学敏感性。在SiHa和SiHa/DDP细胞中，FOXP2与c-MET表达水平呈负相关。机制上，FOXP2与c-MET的启动子区域结合，以负向调节其在CC细胞中的表达。c-MET的过表达可减弱FOXP2过表达引起的DDP诱导的凋亡增强。
这是一项关于FOXP2通过抑制c-MET促进CC细胞对DDP敏感性作用的新研究。本研究中发现的FOXP2/c-MET信号轴可能是CC对DDP治疗耐药的新治疗靶点。
