Zhang Fan, Lv Hui-Zeng, Liu Ji-Ming, Ye Xiao-Yong, Wang Cun-Chuan
Gastrointestinal Surgery Department, the First Affiliated Hospital of Jinan University, 613 Huangpu Avenue West, Guangzhou, 510630 PR China.
Department 1 of General Surgery, the 5th Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, PR China.
Med Sci (Paris). 2018 Oct;34 Focus issue F1:99-104. doi: 10.1051/medsci/201834f117. Epub 2018 Nov 7.
Colon cancer is a common cause of cancer-related death worldwide. However, the underlying mechanism of tumor progression of colon cancer remains far from being elucidated. In the present study, we report the role of UNBS5162 in colon cancer. UNBS5162 is a naphthalimide that can intercalate into DNA and suppress the expression level of CXCL chemokines. Here, we investigated its effect on cell proliferation, mobility and apoptosis in HCT116 cells, and explored the underlying mechanism. A CCK8 assay revealed that UNBS5162 can block the proliferation of colon cancer cells. Base on a Transwell assay, we showed that cell migration and invasion ability of HCT116 cells are inhibited by UNBS5162. In addition, Annexin V-FITC/PI assay and Western blot analysis were performed to detect whether UNBS5162 could induce cell apoptosis. The results indicated that UNBS5162 increases the number of apoptotic cells remarkably. Furthermore, Western blot analysis demonstrated that UNBS5162 down-regulates the expression level of Bcl2, and up-regulates that of Bax as well as the level of activated Caspase-3. Moreover, we examined the impact of UNBS5162 on PI3K/Akt signaling pathway. UNBS5162 substantially inhibited the phosphorylation of Akt and its downstream effector mTOR, and reduced the expression of p-70. Taken together, these results suggest that UNBS5162 should be considered as a potent therapeutic anticancer agent that targets the PI3K/AKT signaling pathway.
结肠癌是全球癌症相关死亡的常见原因。然而,结肠癌肿瘤进展的潜在机制仍远未阐明。在本研究中,我们报告了UNBS5162在结肠癌中的作用。UNBS5162是一种萘酰亚胺,可插入DNA并抑制CXCL趋化因子的表达水平。在此,我们研究了其对HCT116细胞增殖、迁移和凋亡的影响,并探讨了潜在机制。CCK8检测显示UNBS5162可阻断结肠癌细胞的增殖。基于Transwell检测,我们发现UNBS5162抑制了HCT116细胞的迁移和侵袭能力。此外,进行了Annexin V-FITC/PI检测和蛋白质印迹分析,以检测UNBS5162是否能诱导细胞凋亡。结果表明,UNBS5162显著增加了凋亡细胞的数量。此外,蛋白质印迹分析表明,UNBS5162下调了Bcl2的表达水平,上调了Bax的表达水平以及活化的Caspase-3的水平。此外,我们研究了UNBS5162对PI3K/Akt信号通路的影响。UNBS5162显著抑制了Akt及其下游效应物mTOR的磷酸化,并降低了p-70的表达。综上所述,这些结果表明,UNBS5162应被视为一种靶向PI3K/AKT信号通路的强效抗癌治疗药物。