Zhao Hongye, Liu Yongcun, Wu Yunfan, Cheng Jingge, Li Yishuai
The Department of Dermatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
The Department of Surgery, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050011, China.
Cell Biochem Biophys. 2024 Sep;82(3):2387-2399. doi: 10.1007/s12013-024-01349-y. Epub 2024 Jun 14.
ADP ribosylation factor guanylate kinase 1 (ASAP1), a key protein regulating cell migration and invasion, has attracted extensive attention in oncological research in recent years. This study aims to explore the effects of ASAP1 inhibition on lung cancer metastasis and its potential mechanisms, particularly how it modulates the tumor immune microenvironment through the p-STAT3 signaling pathway. In this study, shRNA technology was employed to specifically inhibit ASAP1 expression in lung cancer cell lines A549, NCI-H1299, and PC-9. The effects of ASAP1 inhibition on lung cancer cell viability, apoptosis, migration, and invasion were evaluated using CCK-8, TUNEL apoptosis detection, and cell migration and invasion assays. Furthermore, animal experiments were conducted to assess the in vivo effects of ASAP1 inhibition on lung cancer metastasis, and immunohistochemical analysis was performed to investigate changes in immune cells in lung metastasis models, further exploring its impact on the tumor immune microenvironment. The experimental results demonstrated that ASAP1 inhibition significantly reduced lung cancer cell viability, induced apoptosis in A549, NCI-H1299, and PC-9 cells, and suppressed the migration and invasion abilities of these cells. In vivo experiments revealed that ASAP1 inhibition effectively suppressed lung cancer metastasis and altered the tumor immune microenvironment by regulating immune cells. Moreover, we found that ASAP1 inhibition could decrease tumor cell proliferation and induce tumor apoptosis in lung metastasis models by inhibiting the p-STAT3 signaling pathway. This study confirms that ASAP1 inhibition can suppress lung cancer metastasis by modulating the tumor immune microenvironment through the inhibition of the p-STAT3 signaling pathway. These findings provide new targets for lung cancer treatment and a theoretical basis for developing novel strategies against lung cancer metastasis. Future research will further explore the mechanisms of ASAP1 in lung cancer metastasis and how to optimize treatment strategies for lung cancer patients by targeting ASAP1.
ADP核糖基化因子鸟苷酸激酶1(ASAP1)是一种调节细胞迁移和侵袭的关键蛋白,近年来在肿瘤学研究中受到广泛关注。本研究旨在探讨抑制ASAP1对肺癌转移的影响及其潜在机制,特别是其如何通过p-STAT3信号通路调节肿瘤免疫微环境。在本研究中,采用shRNA技术特异性抑制肺癌细胞系A549、NCI-H1299和PC-9中ASAP1的表达。使用CCK-8、TUNEL凋亡检测以及细胞迁移和侵袭实验评估抑制ASAP1对肺癌细胞活力、凋亡、迁移和侵袭的影响。此外,进行动物实验以评估抑制ASAP1对肺癌转移的体内作用,并进行免疫组化分析以研究肺转移模型中免疫细胞的变化,进一步探索其对肿瘤免疫微环境的影响。实验结果表明,抑制ASAP1可显著降低肺癌细胞活力,诱导A549、NCI-H1299和PC-9细胞凋亡,并抑制这些细胞的迁移和侵袭能力。体内实验表明,抑制ASAP1可有效抑制肺癌转移,并通过调节免疫细胞改变肿瘤免疫微环境。此外,我们发现抑制ASAP1可通过抑制p-STAT3信号通路减少肺转移模型中的肿瘤细胞增殖并诱导肿瘤凋亡。本研究证实,抑制ASAP1可通过抑制p-STAT3信号通路调节肿瘤免疫微环境来抑制肺癌转移。这些发现为肺癌治疗提供了新的靶点,并为开发抗肺癌转移的新策略提供了理论基础。未来的研究将进一步探索ASAP1在肺癌转移中的机制,以及如何通过靶向ASAP1优化肺癌患者的治疗策略。