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Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-12-01 , DOI: 10.1111/jcmm.16134
Lehe Yang 1, 2 , Tianru Zhu 1 , Hua Ye 3 , Yili Shen 2 , Zhiping Li 3 , Luye Chen 3 , Canwei Wang 3 , Xia Chen 3 , Haiyang Zhao 4 , Youqun Xiang 2 , Zhongxiang Xiao 3 , Chengguang Zhao 1, 2, 4 , Jifa Li 3 , Wanle Hu 1
Affiliation  

Colorectal cancer (CRC) accounts for about 10% of all annually diagnosed cancers and cancer‐related deaths worldwide. STAT3 plays a vital role in the occurrence and development of tumours. Gracillin has shown a significant antitumour activity in tumours, but its mechanism remains unknown. The human CRC cell lines HCT116, RKO, and SW480 and immunodeficient mice were used as models to study the effects of gracillin on cell proliferation, migration and apoptosis. These were evaluated by cell viability, colony formation, wound‐healing migration and cell apoptosis assays. Luciferase reporter assay, and immunostaining and western blot analyses were used to explore the specific mechanism through which gracillin exerts its effects. Gracillin significantly reduces viability and migration and stimulates apoptosis in human CRC cells. It also significantly inhibits tumour growth with no apparent physiological toxicity in animal model experiments. Moreover, gracillin is found to inhibit STAT3 phosphorylation and STAT3 target gene products. In addition, gracillin inhibits IL6‐induced nuclear translocation of P‐STAT3. Gracillin shows potent efficacy against CRC by inhibiting the STAT3 pathway. It should be further explored as a unique STAT3 inhibitor for the treatment of CRC.

中文翻译:

Gracillin 通过抑制 STAT3 通路显示出对结直肠癌的有效疗效

结直肠癌 (CRC) 占全球每年诊断出的所有癌症和癌症相关死亡人数的 10% 左右。STAT3在肿瘤的发生发展中起着至关重要的作用。Gracillin 在肿瘤中显示出显着的抗肿瘤活性,但其机制仍不清楚。以人CRC细胞系HCT116、RKO、SW480和免疫缺陷小鼠为模型,研究gracillin对细胞增殖、迁移和凋亡的影响。这些通过细胞活力、集落形成、伤口愈合迁移和细胞凋亡测定来评估。荧光素酶报告基因分析、免疫染色和蛋白质印迹分析用于探索 gracillin 发挥其作用的具体机制。Gracillin 显着降低人类 CRC 细胞的活力和迁移并刺激细胞凋亡。它还显着抑制肿瘤生长,在动物模型实验中没有明显的生理毒性。此外,发现 gracillin 可抑制 STAT3 磷酸化和 STAT3 靶基因产物。此外,gracillin 抑制 IL6 诱导的 P-STAT3 核转位。Gracillin 通过抑制 STAT3 通路显示出对 CRC 的有效功效。应进一步探索它作为治疗 CRC 的独特 STAT3 抑制剂。
更新日期:2021-01-19
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