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

p53 和结直肠癌中的自噬：功能机制和治疗应用

• 批准号: 23591966
• 负责人: MIYAMOTO Yuji
• 金额: $ 3.24万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591966/
• 关键词: 大腸癌; オートファジー; p53; colorectal cancer; colorectal cancer; autophagy; 抗癌剤感受性; 肝転移

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.

自噬是细胞对不利环境和压力的反应。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。目的探讨p53状态和自噬活性对结直肠癌化疗敏感性的影响。1.p53野生型和p53敲低(p53-KD)结直肠癌细胞中DNA损伤诱导自噬。 LC-II在p53-KD细胞中的积累比在p53-cont细胞中更强烈。此外，我们证实，用siATG5处理后，p53-cont和p53-KD细胞中的DNA损伤会诱导细胞凋亡。 p53-KD细胞的凋亡较p53-cont细胞少。2.免疫组化染色显示切除的肝脏肿瘤中一些自噬相关蛋白(Protein A)的表达明显减少。 Protein A高表达组患者与淋巴管炎症相关。

项目成果

Chemotherapy and Targeted Therapy for Patients with Initially Unresectable Colorectal Liver Metastases, Focusing on Conversion Hepatectomy and Long-Term Survival

• DOI: 10.1245/s10434-014-3577-x
• 发表时间: 2014-06-01
• 期刊: ANNALS OF SURGICAL ONCOLOGY
• 影响因子: 3.7
• 作者: Beppu, Toru;Miyamoto, Yuji;Baba, Hideo
• 通讯作者: Baba, Hideo