Cisatracurium regulates the CXCR4/let-7a-5p axis to inhibit colorectal cancer progression by suppressing TGF-β/SMAD2/3 signalling. (25th April 2021)

• Record Type: Journal Article
• Authors: Xia, Yan-Zhi; Shan, Guo-Fa; Yang, Hua; Zha, Jun; Wang, Li; Chen, Jie-Mei; Zhang, Xue-Song
• Is Part Of: Chemico-biological interactions. Volume 339(2021)
• Publication Date: 2021-04-25
• Subjects: Cisatracurium -- CXCR4/let-7a-5p axis -- Colorectal cancer -- TGF-β/SMAD2/3 signalling; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2021.109424
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Objective: To reveal the effects and related mechanism of cisatracurium on colorectal cancer (CRC) development. Methods: HCT116 and SW480 cells were treated with various concentrations of cisatracurium or transforming growth factor-β (TGF-β). Chemokine C-X-C-Motif Receptor 4 (CXCR4) was overexpressed and let-7a-5p was silenced in cells by transfection with pcDNA3.1-CXCR4 or let-7a-5p inhibitor. Cell Counting Kit-8 (CCK-8) assay measured cell viability, and transwell and wound healing assays evaluated cell invasion and migration, respectively. The expression levels of let-7a-5p and CXCR4 were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was conducted to test the levels of CXCR4, TGF-β/SMAD2/3 signalling and metastasis-related proteins. A tumour xenograft assay was performed to assess tumour growth. Results: Cisatracurium treatment suppressed the viability and metastasis of HCT116 and SW480 cells in a concentration-dependent manner, whereas activating TGF-β/SMAD2/3 signalling significantly reversed these effects. Cisatracurium treatment markedly reduced CXCR4 expression by inhibiting TGF-β/SMAD2/3 signalling. Besides, let-7a-5p was identified as a target of CXCR4 and could be upregulated by cisatracurium. Both CXCR4 overexpression and let-7a-5p knockdown alleviated the biological roles of cisatracurium in CRC cells. Moreover, a tumour xenograft assay further confirmed that cisatracurium inhibited tumour growth and metastasis by increasing let-7a-5p expression. Conclusion: Cisatracurium suppressed the viability, metastasis and tumour growth of CRC by regulating the CXCR4/let-7a-5p axis via inhibiting TGF-β/SMAD2/3 signalling. These findings provide a theoretical basis for the role of cisatracurium in the prognosis of CRC patients. Highlights: Cisatracurium suppressed cell viability and metastasis in CRC cell lines. Cisatracurium repressed CRC through inhibition of TGF-β/SMAD2/3 signalling. Cisatracurium reduced CXCR4 level by inhibiting of TGF-β/SMAD2/3 signalling. Cisatracurium enhanced let-7a-5p expression through inhibiting CXCR4. CXCR4/let-7a-5p axis acted as a target of cisatracurium in CRC progress.