UNBS5162 inhibits the proliferation of esophageal cancer squamous cells via the PI3K/AKT signaling pathway

Abstract

C‑X‑C motif chemokine ligand (CXCL) signaling has been demonstrated to be involved in cancer invasion and migration; therefore, CXCL antagonists may serve as anticancer drugs by preventing tumor proliferation. The present study aimed to investigate whether a pan antagonist of CXCLs, UNBS5162, may inhibit esophageal cancer proliferation and to identify the underlying mechanisms. Cell proliferation and cell colony formation results, which were determined by a Cell Counting Kit‑8 assay and crystal violet staining, respectively, demonstrated that UNBS5162 inhibited esophageal cancer cell proliferation. Following treatment with UNBS5162, Transwell migration and Matrigel invasion assays, and flow cytometry with Annexin V‑fluorescein isothiocyanate and propidium iodide staining, were performed to investigate cell migration, invasion and apoptosis in human esophageal cancer cells. The results indicated that invasion and migration was reduced in UNBS5162‑treated cells, while apoptosis was increased. Western blotting experiments confirmed that UNBS5162 downregulated the protein expression of proteins associated with the phosphatidylinositol 3‑kinase (PI3K)/AKT signaling pathway, including the levels of phosphorylated (p)‑AKT, p‑mechanistic target of rapamycin kinase, ribosomal protein S6 kinase β1 and cyclin D1. In addition, upregulated expression of programed cell death 4 was observed following UNBS5162 treatment. The present study demonstrated that UNBS5162 is a novel naphthalimide that may have potential therapeutic use for the prevention of esophageal cancer proliferation and metastasis via the PI3K/AKT signaling pathway.

TRIM27 promotes the development of esophagus cancer via regulating PTEN/AKT signaling pathway

“…Moreover, TRIM14 promotes the activity of PI3K/AKT signaling pathway in osteosarcoma cells [12]. Further, suppressing the PI3K/AKT signaling pathway contributes to inhibiting the proliferation of ESCC cells [13, 14]. However, the detailed relationship between TRIM27 and PI3/AKT pathway remains unclear in human ESCC cells.…”

Long Noncoding RNA LINC00460 Facilitates the Proliferation and Metastasis of Renal Cell Carcinoma via PI3K/AKT Signaling Pathway

“…Emerging literature has identi ed that the PI3K/AKT signaling pathway is crucial for normal cell growth, and its deregulation in uences various cellular responses that are associated with cancer phenotypes, such as cell apoptosis and cell proliferation [35][36][37][38][39][40]. PI3K activation phosphorylates AKT and active AKT can lead to a number of downstream effects including the activation of mTOR, also in the form of phosphorylates mTOR, which in turn directly impacts cell growth and survival [41][42][43].…”

A highly integrated precision nanomedicine strategy to target esophageal squamous cell cancer molecularly and physically

“…Additionally, PI3K/AKT signaling pathway was also reported to associate with the metastasis and chemoresistance of esophageal squamous cell carcinoma[11, 43]. For example, UNBS5162, C-X-C motif chemokine ligand antagonist, was found to inhibited ESCC cell proliferation, invasion, and migration via the PI3K/Akt pathway [44]. Since fluorouracil (5-FU)-resistant esophageal cancer cells overexpressed pAkt, inhibition of PI3K/Akt pathway could reverse the chemoresistance resulting in more cell death [11].…”