Zhuang Ruiying, Liu Haiyan
Jinzhou Medical University, Jinzhou, Liaoning Province, China.
The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China.
Discov Oncol. 2024 Mar 21;15(1):83. doi: 10.1007/s12672-024-00937-x.
The global incidence of endometrial cancer, a malignant tumor in females, is on the rise. It is one of the most common gynecological cancers. Early-stage endometrial cancers can often be treated successfully with uterine extirpation. However, those diagnosed at a later stage have a poor prognosis and encounter treatment challenges. Therefore, additional research is necessary to develop primary prevention strategies for high-risk women and improve survival rates among patients with endometrial cancer. Hence, gene therapy targeting KIF23 shows promise as an advanced strategy for the treatment of endometrial cancer.
Immunohistochemistry, Western blotting, and PCR were used to examine the expression of KIF23 and its associated pathway factors in endometrial cancer tissue (specifically Ishikawa and SNGM cells, respectively). We investigated the functional roles of KIF23 using CCK-8, colony-forming proliferation assays, Transwell migration assays, and xenotransplantation in mice.
Immunohistochemistry analysis showed variations in the expression levels of KIF23 between endometrial cancer tissue and normal endometrium tissue. KIF23 downregulated BAX and caspase-3 protein expression while upregulating BCL-2 protein expression. Additionally, knocking out KIF23 inhibits endometrial cancer cell proliferation and migration while promoting cell death. Mechanistically, our study provides evidence that KIF23 promotes endometrial cancer cell proliferation by activating the ERK and AKT/PI3K pathways, while simultaneously inhibiting programmed cell death in endometrial cancer.
Our study provides evidence to support the inhibition of endometrial cancer by KIF23 knockdown. This offers valuable insights for future research on potential therapeutic strategies for this type of cancer.
子宫内膜癌作为女性恶性肿瘤，其全球发病率呈上升趋势。它是最常见的妇科癌症之一。早期子宫内膜癌通常可通过子宫切除成功治疗。然而，那些在晚期被诊断出的患者预后较差且面临治疗挑战。因此，有必要开展更多研究以制定针对高危女性的一级预防策略，并提高子宫内膜癌患者的生存率。因此，靶向KIF23的基因治疗有望成为治疗子宫内膜癌的一种先进策略。
采用免疫组织化学、蛋白质印迹法和聚合酶链反应分别检测子宫内膜癌组织（具体为Ishikawa细胞和SNGM细胞）中KIF23及其相关通路因子的表达。我们使用CCK-8、集落形成增殖试验、Transwell迁移试验以及小鼠异种移植实验来研究KIF23的功能作用。
免疫组织化学分析显示，子宫内膜癌组织与正常子宫内膜组织中KIF23的表达水平存在差异。KIF23下调BAX和半胱天冬酶-3蛋白表达，同时上调BCL-2蛋白表达。此外，敲除KIF23可抑制子宫内膜癌细胞的增殖和迁移，同时促进细胞死亡。从机制上讲，我们的研究提供了证据表明KIF23通过激活ERK和AKT/PI3K通路促进子宫内膜癌细胞增殖，同时抑制子宫内膜癌中的程序性细胞死亡。
我们的研究为KIF23基因敲低抑制子宫内膜癌提供了证据支持。这为该类型癌症潜在治疗策略的未来研究提供了有价值的见解。
