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CS-NO 通过调节 YAP/TAZ 信号通路抑制抑制糖酵解和胃癌进展。

CS-NO suppresses inhibits glycolysis and gastric cancer progression through regulating YAP/TAZ signaling pathway.

机构信息

The Second Oncology Department, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, Hebei Province, China.

Faculty of Medicine, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia.

出版信息

Cell Biochem Biophys. 2023 Sep;81(3):561-567. doi: 10.1007/s12013-023-01153-0. Epub 2023 Aug 10.

DOI:10.1007/s12013-023-01153-0
PMID:37558859
Abstract

CONTEXT

Gastric cancer (GC) is a significant contributor to global mortality and is recognized for its elevated prevalence and fatality rates. Nitric Oxide (NO) plays a role in multiple aspects of cancer metastasis and progression. CS-NO is a polysaccharide-based biomaterial with NO-releasing properties that shows promising therapeutic potential. Nonetheless, the action mechanism of CS-NO in GC is still largely unclear.

METHODS

The present study employed various experimental techniques, including CCK-8 assay, colony formation assay, EdU staining, and transwell assays, to evaluate the proliferation, migration, and invasion of GC cells. Additionally, ELISA was utilized to measure glucose uptake, lactate production, and cellular ATP levels in GC cells. In vivo investigations on nude mice were conducted to validate the in vitro results.

OBJECTIVE

The present study aimed to examine the potential anti-tumor properties of CS-NO on GC through in vitro and in vivo investigations, while also exploring the underlying mechanisms involved.

RESULTS

Our data suggested that CS-NO might prevent GC cell invasion and migration. Decreased expressions of GLUT1, HK2, and LDHA further demonstrated that CS-NO significantly suppressed aerobic glycolysis in GC cells. The administration of CS-NO resulted in a significant reduction of YAP and TAZ levels in GC cells. Our data further show that CS-NO treatment could inhibit GC cancer growth in mice, consistent with the significant decrease in Ki67, GLUT1 and YAP expression levels.

DISCUSSION AND CONCLUSION

These findings could reveal the good effects of CS-NO therapy on inhibiting GC.

摘要

背景

胃癌(GC)是导致全球死亡率的主要原因之一,其发病率和死亡率都很高。一氧化氮(NO)在癌症转移和进展的多个方面都发挥了作用。CS-NO 是一种具有 NO 释放特性的多糖基生物材料,具有有前景的治疗潜力。然而,CS-NO 在 GC 中的作用机制在很大程度上仍不清楚。

方法

本研究采用了包括 CCK-8 检测、集落形成实验、EdU 染色和 Transwell 实验在内的多种实验技术,以评估 GC 细胞的增殖、迁移和侵袭能力。此外,还通过 ELISA 检测 GC 细胞的葡萄糖摄取、乳酸生成和细胞内 ATP 水平。在裸鼠体内进行了研究,以验证体外结果。

目的

本研究旨在通过体外和体内研究来检验 CS-NO 对 GC 的潜在抗肿瘤特性,并探讨其潜在机制。

结果

我们的数据表明,CS-NO 可能预防 GC 细胞的侵袭和迁移。GLUT1、HK2 和 LDHA 的表达下调进一步表明 CS-NO 显著抑制了 GC 细胞的有氧糖酵解。CS-NO 的给药导致 GC 细胞中 YAP 和 TAZ 水平显著降低。我们的数据还表明,CS-NO 治疗可抑制小鼠 GC 肿瘤的生长,与 Ki67、GLUT1 和 YAP 表达水平的显著下降一致。

讨论与结论

这些发现可能揭示了 CS-NO 治疗抑制 GC 的良好效果。

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Hippo/YAP signaling choreographs the tumor immune microenvironment to promote triple negative breast cancer progression via TAZ/IL-34 axis.
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