Zhai Yan, Lu Qi, Lou Tong, Cao Guangming, Wang Shuzhen, Zhang Zhenyu
Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Ann Transl Med. 2020 Nov;8(22):1494. doi: 10.21037/atm-20-6388.
Ovarian cancer is the 5 most common lethal gynecological malignancy with a 5-year survival rate of about 47% and a localized stage diagnosis of 15%, leading to about 125,000 global deaths each year. Therefore, it is urgent to explore novel and effective strategies for radical cure.
Short hairpin RNA targeting the () gene was used to establish knockdown in ovarian cancer cells. RT-PCR was performed to quantify the expression of mRNA, and western blotting was performed to detect the expression of and epithelial-mesenchymal transition-related proteins. Cell counting kit 8 (CCK8) wound healing and transwell assays were performed to assess cell proliferation and cell invasion. Flow cytometry was used to detect CD80-, CD83-, and CD86-expressing dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) activated by -pulsed DCs.
In this study, we identified as a novel target antigen for immunotherapy against ovarian cancer, which was significantly up regulated in ovarian cancer cells and high-grade ovarian serous adenocarcinoma tissues. knockdown in Ovcar3 cells using short hairpin RNA targeting the gene suppressed the proliferation of migration, invasion, epithelial-mesenchymal transition (EMT), and PI3K/Akt signaling pathway in Ovcar3 cells markedly. significantly up-regulated CD80, CD83, and CD86 (mature makers) expression in DCs and T-cell transformation into CD8 T-cells detected by Flow cytometry.
For malignant ovarian cancer, overexpression promoted cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. pulsing mediated DC maturation and activated CTL response . Our study offers promising DC-based immunotherapy of considerable clinical value for patients with ovarian cancer.
卵巢癌是第五大常见的致命妇科恶性肿瘤，5年生存率约为47%，局部阶段诊断率为15%，每年导致全球约125,000人死亡。因此，迫切需要探索新的有效根治策略。
使用靶向（）基因的短发夹RNA在卵巢癌细胞中建立基因敲低。进行逆转录聚合酶链反应（RT-PCR）以定量基因mRNA的表达，并进行蛋白质印迹法检测和上皮-间质转化相关蛋白的表达。使用细胞计数试剂盒8（CCK8）、伤口愈合和Transwell试验评估细胞增殖和细胞侵袭。采用流式细胞术检测由脉冲树突状细胞（DC）激活的表达CD80、CD83和CD86的树突状细胞（DC）和细胞毒性T淋巴细胞（CTL）。
在本研究中，我们确定为卵巢癌免疫治疗的一种新的靶抗原，其在卵巢癌细胞和高级别卵巢浆液性腺癌组织中显著上调。使用靶向基因的短发夹RNA在Ovcar3细胞中敲低可显著抑制Ovcar3细胞的迁移、侵袭、上皮-间质转化（EMT）和PI3K/Akt信号通路的增殖。通过流式细胞术检测，显著上调了DC中CD80、CD83和CD86（成熟标志物）的表达以及T细胞向CD8 T细胞的转化。
对于恶性卵巢癌，过表达通过PI3K/AKT信号通路促进细胞增殖、迁移和侵袭。脉冲介导DC成熟并激活CTL反应。我们的研究为卵巢癌患者提供了具有相当临床价值的基于DC的免疫治疗方法。
