Silencing Ras-Related C3 Botulinum Toxin Substrate 1 Inhibits Growth and Migration of Hypopharyngeal Squamous Cell Carcinoma via the P38 Mitogen-Activated Protein Kinase Signaling Pathway.

Abstract

BACKGROUND Ras-related C3 botulinum toxin substrate 1 (Rac1) is implicated in a variety of cellular functions and is related to tumor growth and metastasis. This study aimed to explore the role of Rac1 in hypopharyngeal squamous cell carcinoma (HSCC). MATERIAL AND METHODS The Rac1 expression in HSCC tissues was determined by quantitative real-time polymerase chain reaction and Western blot analysis. The level of Rac1 in HSCC cells was downregulated by a Rac1-specific shRNA. Then, the growth and metastasis of HSCC cells were assessed in vitro by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, Hoechst staining, and Transwell assay. Moreover, cells transfected with Rac1 shRNA or negative control were injected subcutaneously into the right axilla of mice, and then the effects of Rac1 silencing on the growth of HSCC were also explored in vivo. Additionally, activation of the P38 mitogen-activated protein kinase (MAPK) signaling pathway was assessed by Western blot. RESULTS Rac1 was highly expressed in HSCC tissues. Silencing Rac1 inhibited the proliferation and cell cycle progress of HSCC cells, and induced their apoptosis. Rac1 silencing also suppressed the migration and invasion of HSCC cells. In vivo study showed that silencing Rac1 suppressed the growth of tumor bodies. Moreover, the P38 MAPK signaling pathway was implicated in the tumor-suppressing effect of Rac1 silencing in vitro and in vivo. CONCLUSIONS Silencing Rac1 suppressed the growth and migration of HSCC through the P38 MAPK signaling pathway. Due to its contribution in HSCC, Rac1 has the potential to become a promising antitumor therapeutic target for HSCC.

• Authors: Huijuan Cheng, Weiwei Wang, Guangke Wang, Anran Wang, Linfang Du, Weihua Lou
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 24 Pg. 768-781 (Feb 07 2018) ISSN: 1643-3750 [Electronic] United States
• PMID: 29410394 (Publication Type: Journal Article)

Chemical References

• RNA, Small Interfering
• p38 Mitogen-Activated Protein Kinases
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9
• rac1 GTP-Binding Protein

Topics

• Animals
• Apoptosis (genetics)
• Carcinoma, Squamous Cell (enzymology, genetics, pathology)
• Cell Cycle Checkpoints (genetics)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Humans
• Hypopharyngeal Neoplasms (enzymology, genetics, pathology)
• MAP Kinase Signaling System
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• RNA, Small Interfering (metabolism)
• Up-Regulation (genetics)
• p38 Mitogen-Activated Protein Kinases (metabolism)
• rac1 GTP-Binding Protein (genetics, metabolism)