30 November 2018 : Laboratory Research
Rho GTPase Activating Protein 24 (ARHGAP24) Regulates the Anti-Cancer Activity of Sorafenib Against Breast Cancer MDA-MB-231 Cells via the Signal Transducer and Activator of Transcription 3 (STAT3) Signaling PathwayXianping Dai1ABE*, Feng Geng1ABC, Jiale Dai2CF, Mengshun Li1ADF, Ming Liu1DEF
Med Sci Monit 2018; 24: LBR8669-8677
BACKGROUND: STAT3 has emerged as a novel potential target for sorafenib, a multikinase inhibitor, in the context of cancer therapy. ARHGAP24 is a Rac-specific Rho GTPase-activating protein (Rho GAP), which can convert Rho GTPases to an inactive state. It has been proved to be an oncosuppressor protein in renal cancer. In the present study, we investigated its anti-cancer effect in breast cancer (BC).
MATERIAL AND METHODS: Quantitative real-time PCR (qRT-PCR) and Western blot analysis were performed to detect the expression of ARHGAP24 in clinical tissue samples. Then, BC MDA-MB-231 cells were virally transduced with ARHGAP24 silencing or overexpression lentiviral vectors in the absence or presence of sorafenib. Cell viability and metastatic ability were evaluated by using the Cell Counting Kit-8 (CCK-8) and Transwell assays. Proteins belonging to the STAT3 pathway were detected by Western blot.
RESULTS: ARHGAP24 decreased in BC tissues compared with the adjacent normal tissues. Forced expression of ARHGAP24 and sorafenib treatment significantly suppressed the viability, migration, and invasion of MDA-MB-231 cells. Conversely, elimination of the endogenous ARHGAP24 with shRNA promoted cell viability, migration, and invasion. The phosphorylation of STAT3 and the expression of MMP-2 and MMP-9 were attenuated by ARHGAP24 ectopic expression and sorafenib treatment. Furthermore, forced expression of ARHGAP24 significantly enhanced sorafenib-induced decrease of cell viability, migration, and invasion of MDA-MB-231 cells, while elimination of the endogenous ARHGAP24 with shRNA inhibited it.
CONCLUSIONS: ARHGAP24 can suppress the development of MDA-MB-231 cells via the STAT3 signaling pathway, and sorafenib inhibits cell viability, migration, invasion, and STAT3 activation in MDA-MB-231 cells through ARHGAP24.
Keywords: STAT3 Transcription Factor
12 September 2022 : EditorialEditorial: Treatment with Dual Incretin Receptor Agonists to Maintain Normal Glucose Levels May Also Maintain Normal Weight and Control Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)
Med Sci Monit 2022; 28:e938365
16 September 2022 : Review articleEffects of Physiotherapy on Rehabilitation and Quality of Life in Patients Hospitalized for COVID-19: A Rev...
Med Sci Monit In Press; DOI: 10.12659/MSM.938141
12 September 2022 : Clinical ResearchEffect of Vitamin D Concentration on Course of COVID-19
Med Sci Monit In Press; DOI: 10.12659/MSM.937741
29 August 2022 : Database AnalysisTranscriptome Analysis of Peripheral Blood Mononuclear Cells Response in Patients with Severe COVID-19 Reve...
Med Sci Monit 2022; 28:e937532
26 Sep 2022 : Clinical ResearchDistribution and Determinants of Plasma Homocysteine Levels in a Preconception Population: A Retrospective ...
Med Sci Monit In Press; DOI: 10.12659/MSM.937987
26 Sep 2022 : Clinical ResearchLatency and Interpeak Interval Values of Auditory Brainstem Response in 73 Individuals with Normal Hearing
Med Sci Monit In Press; DOI: 10.12659/MSM.937847
23 Sep 2022 : Review articleA Review of the Role of Ultrasound Radiomics and Its Application and Limitations in the Investigation of Th...
Med Sci Monit In Press; DOI: 10.12659/MSM.937738
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292