Inhibition of ASAP1 Modulates the Tumor Immune Microenvironment and Suppresses Lung Cancer Metastasis via the p-STAT3 Signaling Pathway.

Abstract

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.