Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui, China.
Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):397-404. doi: 10.26355/eurrev_201801_14187.
Liver cancer emerged as a major health problem, and it accounts for leading cancer-related death worldwide. Due to recurrence and metastatic behavior, it is challenging to be controlled and managed. Understanding the regulative role of different proteins, which regulates liver cancer in various pathological stages, is essential to be investigated. In this study, we analyzed the correlation between Foxa1 suppression along with apoptosis and cancer stem cell proliferation.
CD133+ cells were used to induce the initial and advanced stage of liver cancer. Histology was used to study and confirm the tissue complications associated with initial, advanced and Foxa1 silenced liver cancer tissues. Immunohistochemistry and Western blotting were used to quantify Foxa1, CD133 expression. TUNEL assay was performed to study apoptosis.
Initially using CD133+ cells, we successfully developed a mouse model with the initial and advanced stage of liver cancer upon 4 and 8 weeks incubation. Histologically, as the tumor progress, it shows more proliferative cells with disorganized tissue structure. Foxa1 silencing aids in recovering from initial liver cancer, but it has only limited effects with advanced liver cancer. The apoptosis process is enhanced in initial liver cancer, and Foxa1 silenced tissue when compared with the advanced stage of liver cancer. Foxa1 silencing also suppresses the cancer stem cell proliferation.
Overall, our results reveal the critical role of Foxa1 in regulating apoptosis and liver cancer stem cells.
肝癌已成为一个主要的健康问题，它是全球导致癌症相关死亡的主要原因。由于其复发和转移行为，肝癌的控制和管理具有挑战性。了解不同蛋白质在各种病理阶段对肝癌的调节作用，对于研究肝癌至关重要。在本研究中，我们分析了 Foxa1 抑制与细胞凋亡和癌症干细胞增殖之间的相关性。
使用 CD133+细胞诱导肝癌的早期和晚期阶段。通过组织学研究和确认与肝癌早期、晚期和 Foxa1 沉默组织相关的组织并发症，来研究组织学变化。通过免疫组织化学和 Western blot 定量检测 Foxa1 和 CD133 的表达。通过 TUNEL 检测来研究细胞凋亡。
最初使用 CD133+细胞，我们成功地在 4 周和 8 周孵育后，在小鼠模型中建立了肝癌的早期和晚期阶段。组织学上，随着肿瘤的进展，显示出更多具有紊乱组织结构的增殖细胞。Foxa1 沉默有助于从肝癌早期恢复，但对晚期肝癌的效果有限。与晚期肝癌相比，早期肝癌和 Foxa1 沉默组织中的细胞凋亡过程增强。Foxa1 沉默还抑制了癌症干细胞的增殖。
总的来说，我们的结果揭示了 Foxa1 在调节细胞凋亡和肝癌干细胞中的关键作用。
