Eur Rev Med Pharmacol Sci 2019; 23 (13): 5840-5850

DOI: 10.26355/eurrev_201907_18326

ARHGAP15 regulates lung cancer cell proliferation and metastasis via the STAT3 pathway

Z.-D. Liu, Z.-X. Mou, X.-H. Che, K. Wang, H.-X. Li, X.-Y. Chen, X.-M. Guo

Oncology Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong, China. 673953316@qq.com


OBJECTIVE: Lung cancer, which is typically diagnosed at later stages, is a leading cause of cancer death among both males and females given its highly invasive and rapidly metastasizing nature. Rho GTPase activating protein 15 (ARHGAP15) is a member of the RhoGAP family and functions in multiple biological processes, such as cell proliferation and migration. However, the effect of ARHGAP15 in lung cancer and its underlying molecular mechanisms remain unclear.

PATIENTS AND METHODS: In this study, immunohistochemistry and Real Time PCR were performed to detect ARHGAP15 expression in lung cancer tissues and cells. Proliferation, transwell, and Western blot assays were further performed to explore the role and underlying mechanism of ARHGAP15 in lung cancer.

RESULTS: Reduced ARHGAP15 expression was observed in lung cancer tissues and cells. In vitro upregulation of ARHGAP15 in lung cancer cells strongly suppressed cell proliferation, migration, and invasion and was accompanied by reduced matrix metalloproteinase-2 (MMP2), MMP9, vascular endothelial growth factor (VEGF) expression, and the phosphorylation of the signal transducer and activator of transcription-3 (p-STAT3). In contrast, interleukin-6 (IL-6) had the opposite effect and the induction of IL-6 was counteracted by ARHGAP15 upregulation. In addition, the proliferation, migration, and cell invasion induced by ARHGAP15 silencing were potentially inhibited by the STAT3 inhibitor AG490 (100 ┬ÁM), MMP2, MMP9, VEGF, and p-STAT3 levels decreased.

CONCLUSIONS: These results suggest that ARGFAP15 suppressed the proliferation and metastasis of lung cancer cells, which may occur through the inhibition of MMP2, MMP9, and VEGF expression via the STAT3 pathway inactivation.

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To cite this article

Z.-D. Liu, Z.-X. Mou, X.-H. Che, K. Wang, H.-X. Li, X.-Y. Chen, X.-M. Guo
ARHGAP15 regulates lung cancer cell proliferation and metastasis via the STAT3 pathway

Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 13
Pages: 5840-5850
DOI: 10.26355/eurrev_201907_18326