Abstract
BackgroundPancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers. In this study, we aimed to investigate the function of Rho GTPase-activating protein 30 (ARHGAP30) in pancreatic cancer cells and thus propose a novel therapy for pancreatic cancer.MethodsARHGAP30 expression in tumor tissues from patients with pancreatic cancer as well as cell lines was detected using immunohistochemistry (IHC), real-time polymerase chain reaction, and western blotting. Cell proliferation, transwell, and apoptosis assays were performed and the levels of related proteins were determined after ARHGAP30 knockdown or overexpression. Additionally, in vivo experiments were performed on nude mice.ResultsARHGAP30 expression was found to be significantly increased in tumor tissues from patients with pancreatic cancer as well as in pancreatic cancer cell lines. IHC and prognostic analyses indicated that patients with high ARHGAP30 expression had a good prognosis. ARHGAP30 overexpression significantly decreased pancreatic cancer cell proliferation and metastasis; promoted apoptosis; reduced β-catenin, B-cell lymphoma 2 (Bcl-2), matrix metalloproteinase-2 (MMP2), and MMP9 expression; and increased Bcl-2-associated X protein (Bax) and cleaved caspase-3 expression. ARHGAP30 knockdown elicited the opposite effects. The effects of ARHGAP30 knockdown were potently attenuated by the β-catenin inhibitor XAV939. ARHGAP30 knockdown-induced RHOA activity was potently attenuated by the RHOA inhibitor CCG1423. In vivo, ARHGAP30 overexpression significantly inhibited lung metastasis in nude mice and increased the survival of mice with lung metastases.ConclusionsOur findings indicate that ARHGAP30 may function as a tumor suppressor in pancreatic cancer progression by regulating the expression of related genes and the β-catenin pathway.
Highlights
Pancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers
ARHGAP30 expression was significantly decreased in tumor tissues of patients with pancreatic cancer and pancreatic cancer cell lines ARHGAP30 expression in 30 paired cancer and adjacent tissues from patients with pancreatic cancer was analyzed using Real-time polymerase chain reaction (RT-PCR)
We found that ARHGAP30 protein expression was lower in pancreatic cancer tissues than in adjacent tissues (Fig. 1b)
Summary
Pancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers. We aimed to investigate the function of Rho GTPase-activating protein 30 (ARHGAP30) in pancreatic cancer cells and propose a novel therapy for pancreatic cancer. Pancreatic cancer has been reported as the fourth leading cause of cancer-related death in the United States [1]. This malignancy is extremely difficult to cure, Zhou et al Cancer Cell Int (2020) 20:225 with a 5-year overall survival rate of < 5%, and treatment mainly involves surgery combined with radiotherapy and chemotherapy [2, 3]. This study aimed to investigate the role and potential mechanism of ARHGAP30 in pancreatic cancer cells
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