BackgroundCervical cancer is the third most common gynecological malignancy. Conventional treatment options are known to be ineffective for the majority of patients with advanced or recurrent cervical cancer. Therefore, novel therapeutic agents for cervical cancer are necessary. In this study, the effects of CKD-602 in cervical cancer were investigated.MethodsThree established human, immortalized, cervical cancer cell lines (CaSki, HeLa and SiHa) were used in this study. Following treatment with CKD-602, apoptosis was quantified using fluorescein isothiocyanate Annexin V-FITC and propidium iodide (PI) detection kit and cell cycle analysis was analyzed using fluorescence activated cell sorting (FACS). Transwell chambers were used for invasion assays. Western blot assay was performed to analyze proteomics. CaSki cells were subcutaneously injected into BALB/c-nude mice and cervical cancer xenograft model was established to elucidate the antitumor effect of CKD-602 in vivo.ResultsTreatment with CKD-602 induced apoptosis and increased expression of the enzyme PARP, cleaved PARP, and BAX. In addition, expression of phosphorylated p53 increased. Cell cycle arrest at G2/M phase and inhibition of invasion were detected after treatment with CKD-602. A significant decrease in cervical cancer tumor volume was observed in this in vivo model, following treatment with CKD-602.ConclusionsThis is the first report of CKD-602 having an antitumor effect in cervical cancer in both an in vitro and in vivo models. The results of this study indicate that CKD-602 may be a novel potential drug, targeting cervical cancer, providing new opportunities in the development of new therapeutic strategies.

中文翻译：

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CKD-602 是一种拓扑异构酶 I 抑制剂，可诱导细胞凋亡和细胞周期停滞并抑制宫颈癌侵袭

背景宫颈癌是第三常见的妇科恶性肿瘤。已知常规治疗方案对大多数晚期或复发性宫颈癌患者无效。因此，需要新的宫颈癌治疗剂。在本研究中，研究了CKD-602在宫颈癌中的作用。方法本研究中使用了三种已建立的人、永生化宫颈癌细胞系（CaSki、HeLa和SiHa）。用 CKD-602 处理后，使用异硫氰酸荧光素膜联蛋白 V-FITC 和碘化丙啶 (PI) 检测试剂盒量化细胞凋亡，并使用荧光激活细胞分选 (FACS) 分析细胞周期分析。Transwell 室用于侵袭测定。进行蛋白质印迹分析以分析蛋白质组学。将 CaSki 细胞皮下注射到 BALB/c 裸鼠体内，建立宫颈癌异种移植模型，阐明 CKD-602 的体内抗肿瘤作用。巴克斯。此外，磷酸化 p53 的表达增加。用 CKD-602 处理后检测到 G2/M 期的细胞周期停滞和侵袭抑制。在用CKD-602治疗后，在该体内模型中观察到宫颈癌肿瘤体积显着减少。结论这是CKD-602在体外和体内模型中对宫颈癌具有抗肿瘤作用的首次报道。本研究结果表明，CKD-602可能是一种新型潜在药物，针对宫颈癌，