AIM2 regulates viability and apoptosis in human colorectal cancer cells via the PI3K/Akt pathway.
AIM2 regulates viability and apoptosis in human colorectal cancer cells via the PI3K/Akt pathway.
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DOI：
10.2147/ott.s125039
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发表时间：
2017
影响因子：
4
通讯作者：
Yu S
中科院分区：
文献类型：
--
作者：
Chen J;Wang Z;Yu S
在黑色素瘤中缺失2（AIM 2）作为细胞质中的DNA传感器在先天免疫中起重要作用，其通过触发AIM 2炎性体的组装而导致半胱天冬酶-1介导的炎症反应和细胞死亡。近年来，研究表明AIM 2可以抑制癌细胞增殖，并且在大肠癌（CRC）患者中经常发现编码AIM 2的基因突变。然而，AIM 2限制肿瘤生长的机制仍不清楚。我们通过慢病毒转染在HCT 116 CRC细胞中重建AIM 2表达。MTT法和流式细胞仪检测结果表明，AIM 2的表达抑制了大肠癌细胞的存活率，增加了大肠癌细胞的凋亡率，细胞周期分析表明AIM 2阻断了大肠癌细胞由G1期向S期的转变。Western blot分析显示AIM 2通过抑制磷脂酰肌醇3-激酶（PI 3 K）/蛋白激酶B（Akt）途径促进CRC细胞凋亡。我们的数据表明，AIM 2作为肿瘤抑制因子发挥着关键作用，并可能成为CRC的潜在治疗靶点。
Absent in melanoma 2 (AIM2) plays an important role in innate immunity as a DNA sensor in the cytoplasm by triggering the assembly of an AIM2 inflammasome that results in caspase-1-mediated inflammatory responses and cell death. In recent years, studies have indicated that AIM2 can suppress cancer cell proliferation, and mutations in the gene encoding AIM2 are frequently identified in patients with colorectal cancer (CRC). However, the mechanism by which AIM2 restricts tumor growth remains unclear. We reconstructed AIM2 expression in HCT116 CRC cells by lentivirus transfection. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, we demonstrated that expression of AIM2 inhibited the viability and increased the apoptosis rate of CRC cells, and cell cycle analysis suggested that AIM2 blocked cell cycle transition from G1 to S phase. Western blot analysis showed that AIM2 promoted apoptosis in CRC cells by suppressing the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Our data suggest that AIM2 plays a critical role as a tumor suppressor and might serve as a potential therapeutic target in CRC.