GABA regulates the proliferation and apoptosis of head and neck squamous cell carcinoma cells by promoting the expression of CCND2 and BCL2L1.

Gamma-aminobutyric acid (GABA) is a multifunctional molecule that is widely present in the nervous system and nonneuronal tissues. It plays pivotal roles in neurotransmission, regulation of secretion, cell differentiation, proliferation, and tumorigenesis. However, the exact mechanisms of GABA in head and neck squamous cell carcinomas (HNSCCs) are unknown. We took advantage of RNA sequencing in this work and uncovered the potential gene expression profiles of the GABA-treated HNSCC cell line HN4-2. We found that the expression of CCND2 and BCL2L1 was significantly upregulated. Furthermore, GABA treatment inhibited the cell apoptosis induced by cisplatin and regulated the cell cycle after treatment with cisplatin in HN4-2 cells. Moreover, we also found that GABA could upregulate the expression of CCND2 and BCL2L1 after treatment with cisplatin. Our results not only reveal the potential pro-tumorigenic effect of GABA on HNSCCs but also provide a novel therapeutic target for HNSCC treatment.

Utilizing ICG Spectroscopical Properties for Real-Time Nanoparticle Release Quantification In vitro and In vivo in Imaging Setups.

BACKGROUND: Nanoparticle imaging and tracking the release of the loaded material from the nanoparticle system have attracted significant attention in recent years. If the release of the loaded molecules could be monitored reliably in vivo, it would speed up the development of drug delivery systems remarkably. METHODS: Here, we test a system that uses indocyanine green (ICG) as a fluorescent agent for studying release kinetics in vitro and in vivo from the lipid iron nanoparticle delivery system. The ICG spectral properties like its concentration dependence, sensitivity and the fluctuation of the absorption and emission wavelengths can be utilized for gathering information about the change of the ICG surrounding. RESULTS: We have found that the absorption, fluorescence, and photoacoustic spectra of ICG in lipid iron nanoparticles differ from the spectra of ICG in pure water and plasma. We followed the ICG containing liposomal nanoparticle uptake into squamous carcinoma cells (SCC) by fluorescence microscopy and the in vivo uptake into SCC tumors in an orthotopic xenograft nude mouse model under a surgical microscope. CONCLUSION: Absorption and emission properties of ICG in the different solvent environment, like in plasma and human serum albumin, differ from those in aqueous solution. Photoacoustic spectral imaging confirmed a peak shift towards longer wavelengths and an intensity increase of ICG when bound to the lipids. The SCC cells showed that the ICG containing liposomes bind to the cell surface but are not internalized in the SCC-9 cells after 60 minutes of incubation. We also showed here that ICG containing liposomal nanoparticles can be traced under a surgical camera in vivo in orthotopic SCC xenografts in mice.

MiR-149-5p regulates cisplatin chemosensitivity, cell growth, and metastasis of oral squamous cell carcinoma cells by targeting TGFß2.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a public health problem worldwide. MicroRNAs, acting as either oncogenes or tumor suppressors, have gathered much attention. The aim of this study was to characterize the role of miR-149-5p in drug resistance, cell growth, and metastasis and its underlying mechanism in oral squamous cell carcinoma. METHODS: The expressions of miR-149-5p and TGFß2 were measured by quantitative real-time polymerase chain reaction. The survival rate of cells treated with different concentrations of CDDP was checked by CCK-8. The cell proliferation and apoptosis was determined by CCK-8 and flow cytometry, respectively. Cell migration and invasion were examined using transwell assay. The interaction of miR-149-5p and TGFß2 was predicted by online software Targetscan and confirmed by luciferase reporter assay. The protein expression of TGFß2, p-SMAD2 and p-SMAD3 was quantified using western blot. RESULTS: The expression of miR-149-5p was obviously decreased in OSCC tissues and cell lines, and its expression was lower in a cisplatin resistant cell line (CAL-27/CDDP) than that of a normal OSCC cell line (CAL-27). CCK-8 assay suggested that miR-149-5p increased drug sensitivity in CAL-27 and CAL-27/CDDP cells. miR-149-5p attenuated proliferation, migration and invasion, and promoted apoptosis of CAL-27 and CAL-27/CDDP cells. In addition, TGFß2 was up-regulated in OSCC cells at both mRNA and protein levels. Moreover, miR-149-5p promoted cisplatin chemosensitivity and regulated cell proliferation, apoptosis, migration and invasion by targeting TGFß2 in CAL-27 and CAL-27/CDDP cells. CONCLUSION: miR-149-5p regulates cisplatin chemosensitivity, cell growth, apoptosis and metastasis by targeting TGFß2. miR-149-5p/TGFß2 axis has potential for therapy of OSCC.