p53 and autophagy in colorectal cancer : function mechanism and Therapeutic applications

自噬是一种对不利环境和压力的细胞反应。最近的证据表明，肿瘤细胞在抗癌药物治疗过程中会诱导自噬。然而，这些事件对癌症的影响尚不清楚。本研究的目的是评价P53基因状态和自噬活性对结直肠癌化疗敏感性的影响。1.DNA损伤诱导P53野生型和P53基因敲除(P53-KD)结直肠癌细胞自噬。在P53-KD细胞中，LC-II的积聚比在P53-CONT细胞中更强。此外，我们还证实了siATG5处理后的P53-CONT和P53-KD细胞发生了DNA损伤，诱导了细胞的凋亡。P53-KD细胞的凋亡率低于P53-CONT细胞。2.切除的肝肿瘤免疫组织化学染色显示，某些自噬相关蛋白(蛋白A)的表达明显减少。A蛋白高表达组与淋巴侵袭有关。

Autophagy is a celluar response to adverse environment and stress. Recent evidence suggests that tumor cells induce autophagy during treatment of anticancer drugs. However, the effect of these events on cancer is not known. The aime was to evaluate the effect of p53 status and autophagy activity on the chemosensitivity of colorectal cancer.1.Autophagy was induced in response to DNA damage in p53 wild-type and p53 knockdown(p53-KD) colorectal cancer cells. The accumulation of LC-II was more intense in p53-KD cell than that in p53-cont cell. Furtheremore, we confirmed that apoptosis was induced in response to DNA damage in p53-cont and p53-KD cells after treating with siATG5. Apoptosis in p53-KD cell was less than that in p53-cont cell.2.Immunohistochemical staining of resected liver tumor revealed that hte expression of some autophagic related protein(Protein A) was markedly decreased. Patients in high Protein A expression group was associated with lymphphatic invation.