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将膜联蛋白A1作为可成药靶点，通过自噬途径增强厚朴酚在结肠癌中的抗肿瘤作用。

Targeting Annexin A1 as a Druggable Player to Enhance the Anti-Tumor Role of Honokiol in Colon Cancer through Autophagic Pathway.

作者信息

Wang Xi, Shao Gang, Hong Xiangyu, Shi Yue, Zheng Yiting, Yu Yucheng, Fu Caiyun

机构信息

Department of Oncology, No.903 Hospital of PLA Joint Logistic Support Force, Hangzhou 310013, China.

Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.

出版信息

Pharmaceuticals (Basel). 2023 Jan 1;16(1):70. doi: 10.3390/ph16010070.

DOI:10.3390/ph16010070
PMID:36678567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9862434/
Abstract

Colon cancer is one of the most common digestive tract malignancies, having the second highest mortality rate among all tumors, with a five-year survival of advanced patients of only 10%. Efficient, targeted drugs are still lacking in treating colon cancer, so it is urgent to explore novel druggable targets. Here, we demonstrated that annexin A1 (ANXA1) was overexpressed in tumors of 50% of colon cancer patients, and ANXA1 overexpression was significantly negatively correlated with the poor prognosis of colon cancer. ANXA1 promoted the abnormal proliferation of colon cancer cells in vitro and in vivo by regulating the cell cycle, while the knockdown of ANXA1 almost totally inhibited the growth of colon cancer cells in vivo. Furthermore, ANXA1 antagonized the autophagic death of honokiol in colon cancer cells via stabilizing mitochondrial reactive oxygen species. Based on these results, we speculated that ANXA1 might be a druggable target to control colon cancer and overcome drug resistance.

摘要

结肠癌是最常见的消化道恶性肿瘤之一，在所有肿瘤中死亡率排名第二，晚期患者的五年生存率仅为10%。治疗结肠癌仍缺乏有效的靶向药物，因此探索新的可成药靶点迫在眉睫。在此，我们证明50%的结肠癌患者肿瘤中膜联蛋白A1（ANXA1）过表达，且ANXA1过表达与结肠癌的不良预后显著负相关。ANXA1通过调节细胞周期促进体外和体内结肠癌细胞的异常增殖，而敲低ANXA1几乎完全抑制体内结肠癌细胞的生长。此外，ANXA1通过稳定线粒体活性氧拮抗厚朴酚诱导的结肠癌细胞自噬死亡。基于这些结果，我们推测ANXA1可能是控制结肠癌和克服耐药性的一个可成药靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/76ee245eb59d/pharmaceuticals-16-00070-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/2fb7e594c1e6/pharmaceuticals-16-00070-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/0bb896ebcfa1/pharmaceuticals-16-00070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/228b212fd299/pharmaceuticals-16-00070-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/96f208991a0b/pharmaceuticals-16-00070-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/61f9697daf8c/pharmaceuticals-16-00070-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/76ee245eb59d/pharmaceuticals-16-00070-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/2fb7e594c1e6/pharmaceuticals-16-00070-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/0bb896ebcfa1/pharmaceuticals-16-00070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/228b212fd299/pharmaceuticals-16-00070-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/96f208991a0b/pharmaceuticals-16-00070-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/61f9697daf8c/pharmaceuticals-16-00070-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7392/9862434/76ee245eb59d/pharmaceuticals-16-00070-g006.jpg

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