Tian Xia, Han Zheng, Zhu Qingxi, Tan Jie, Liu Weijie, Wang Yanfen, Chen Wei, Zou Yanli, Cai Yishan, Huang Shasha, Chen Aifang, Zhan Ting, Huang Min, Liu Meng, Huang Xiaodong
Department of Gastroenterology, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, 430060, China.
Department of Gastroenterology, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, 430060, China.
Biomed Pharmacother. 2018 Dec;108:331-337. doi: 10.1016/j.biopha.2018.09.020. Epub 2018 Sep 15.
Cadherin-17 (CDH17), a structurally unique member of the non-classical cadherin family, is associated with poor survival, cell proliferation, and metastasis in colorectal cancer. However, the role of CDH17 in the apoptosis and autophagy of colorectal cancer cells remains unclear. Here, we aimed to investigate the effect of CDH17 knockdown on autophagy and apoptosis in colorectal cancer cells. We inhibited CDH17 expression in KM12SM and KM12C colorectal cancer cells by RNA interference and found that silencing of CDH17 significantly inhibited cell viability and increased apoptosis in KM12SM and KM12C cells. In addition, silencing of CDH17 significantly increased the expression of cleaved caspase-3 and Bax and decreased the expression of Bcl-2. Concurrently, silencing of CDH17 significantly inhibited the conversion of LC3-I to LC3-II and decreased the formation of LC3 autophagic vacuoles and the accumulation of acidic vesicular organelles, indicating that autophagy was significantly inhibited in KM12SM and KM12C cells. Additionally, treatment with the autophagy-specific activator rapamycin attenuated apoptosis in CDH17-knockdown cells and as indicated by decreased caspase-3 activity, decreased expression of cleaved caspase-3 and Bax, and increased expression of Bcl-2. In conclusion, CDH17 silencing induced apoptosis and inhibited autophagy in KM12SM and KM12C cells, and this autophagy protected the cells from apoptotic cell death.
钙黏蛋白-17（CDH17）是非经典钙黏蛋白家族中结构独特的成员，与结直肠癌患者的不良预后、细胞增殖和转移相关。然而，CDH17在结直肠癌细胞凋亡和自噬中的作用仍不清楚。在此，我们旨在研究敲低CDH17对结直肠癌细胞自噬和凋亡的影响。我们通过RNA干扰抑制了KM12SM和KM12C结直肠癌细胞中CDH17的表达，发现敲低CDH17可显著抑制KM12SM和KM12C细胞的活力并增加其凋亡。此外，敲低CDH17可显著增加裂解的半胱天冬酶-3和Bax的表达，并降低Bcl-2的表达。同时，敲低CDH17可显著抑制LC3-I向LC3-II的转化，减少LC3自噬泡的形成以及酸性囊泡细胞器的积累，表明KM12SM和KM12C细胞中的自噬被显著抑制。此外，用自噬特异性激活剂雷帕霉素处理可减轻CDH17敲低细胞中的凋亡，表现为半胱天冬酶-3活性降低、裂解的半胱天冬酶-3和Bax表达降低以及Bcl-2表达增加。总之，敲低CDH17可诱导KM12SM和KM12C细胞凋亡并抑制自噬，且这种自噬可保护细胞免于凋亡性细胞死亡。
