Wang Yanqing, Yang Xiao, Xian Shu, Zhang Li, Cheng Yanxiang
Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Oncol Lett. 2019 Jul;18(1):298-306. doi: 10.3892/ol.2019.10306. Epub 2019 May 3.
Ovarian cancer (OC) has the worst prognosis among all malignancy types in females worldwide according to epidemiological studies in 2017. Although radiotherapy, chemotherapy and surgical treatment are the most common treatment methods, their curative effects are not satisfactory. The present study aimed to examine the role of cluster of differentiation 44 variant 6 (CD44v6) in the molecular mechanism of the proliferation and tumorigenicity of OC cells, and provide a novel target for the clinical treatment of OC. A total of 46 clinical samples were collected, including 24 malignant ovarian tumor tissue samples and 22 benign ovarian tissue samples. Expression of CD44v6 and nuclear factor-κB (NF-κB) in these samples was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The A2780 OC cell line was used to establish a normal control group, a negative control group and a CD44v6-small interfering (si)RNA transfection group. The expression of CD44v6 and NF-κB mRNA was detected in each group by RT-qPCR. The proliferation, invasion and migration abilities of the cells were then assessed by Transwell and colony formation assays. Additionally, immunofluorescence was used to detect nuclear NF-κB expression. CD44v6 and NF-κB mRNA expression levels were significantly increased in malignant ovarian tumor tissues, compared with normal ovarian tissues (P<0.01), and immunohistochemistry demonstrated similar results. In the CD44v6-siRNA group, NF-κB mRNA expression was significantly reduced, compared with the control and negative control (both P<0.01) groups. Transwell and colony formation assays demonstrated that the migration, invasion and colony formation abilities of OC cells in the CD44v6-siRNA group were significantly reduced, compared with the control and negative control (both P<0.01) groups. Immunofluorescence results demonstrated that the expression of NF-κB in the cytoplasm and nucleus of the CD44v6-siRNA group was also markedly reduced, compared with the other two groups. In conclusion, CD44v6 may participate in the proliferation of OC cells through activation of the NF-κB pathway and these observations may provide a novel therapeutic target for the clinical treatment of OC.
根据2017年的流行病学研究,卵巢癌(OC)在全球女性所有恶性肿瘤类型中预后最差。尽管放疗、化疗和手术治疗是最常见的治疗方法,但其疗效并不令人满意。本研究旨在探讨分化簇44变体6(CD44v6)在OC细胞增殖和致瘤性分子机制中的作用,并为OC的临床治疗提供新的靶点。共收集46份临床样本,包括24份恶性卵巢肿瘤组织样本和22份良性卵巢组织样本。通过逆转录定量聚合酶链反应(RT-qPCR)和免疫组织化学检测这些样本中CD44v6和核因子-κB(NF-κB)的表达。使用A2780 OC细胞系建立正常对照组、阴性对照组和CD44v6小干扰(si)RNA转染组。通过RT-qPCR检测每组中CD44v6和NF-κB mRNA的表达。然后通过Transwell和集落形成试验评估细胞的增殖、侵袭和迁移能力。此外,采用免疫荧光检测细胞核NF-κB的表达。与正常卵巢组织相比,恶性卵巢肿瘤组织中CD44v6和NF-κB mRNA表达水平显著升高(P<0.01),免疫组织化学也显示了类似结果。在CD44v6-siRNA组中,与对照组和阴性对照组相比,NF-κB mRNA表达显著降低(均P<0.01)。Transwell和集落形成试验表明,与对照组和阴性对照组相比,CD44v6-siRNA组中OC细胞的迁移、侵袭和集落形成能力显著降低(均P<0.01)。免疫荧光结果表明,与其他两组相比,CD44v6-siRNA组细胞质和细胞核中NF-κB的表达也明显降低。总之,CD44v6可能通过激活NF-κB途径参与OC细胞的增殖,这些观察结果可能为OC的临床治疗提供新的治疗靶点。