scholarly journals NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression

2021 ◽  
Vol 22 (20) ◽  
pp. 11108
Author(s):  
Sarah Adriana Scuderi ◽  
Giovanna Casili ◽  
Rossella Basilotta ◽  
Marika Lanza ◽  
Alessia Filippone ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Nlrp3 Inflammasome ◽  
P53 Expression

Oral cancer is one of the most common human malignancies, and its incidence is increasing worldwide. In particular, oral squamous cell carcinoma (OSCC) is characterized by high rates of proliferation, invasiveness, and metastasis. Currently, standard treatment for OSCC includes surgical removal, chemotherapy, and radiotherapy; however, the survival rate of patients with OSCC remains low, thus new therapies are needed. It has been proven that excessive NLRP3 inflammasome activation and apoptosis alteration may contribute to oral cancer progression. This study aimed to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in an in vitro and in vivo xenograft model of oral cancer. In vitro results revealed that BAY-117082 at concentrations of 5, 10, and 30 µM was able to reduce OSCC cell viability. BAY-117082 at higher concentrations significantly reduced NLRP3, ASC, caspase-1, IL-1β, and IL-18 expression. Moreover, Bax, Bad, and p53 expression were increased, whereas Bcl-2 expression was reduced. Furthermore, the in vivo study demonstrated that BAY-117082 at doses of 2.5 and 5 mg/kg significantly decreased subcutaneous tumor mass, and also reduced NLRP3 inflammasome pathway activation. Therefore, based on these results, the use of BAY-117082 could be considered a promising strategy to counteract oral cancer progression, thanks its ability to modulate the NLRP3 inflammasome and apoptosis pathways.

Dlx5 promotes cancer progression through regulation of CCND1 in oral squamous cell carcinoma (OSCC)

2021 ◽  
pp. 1-11
Author(s):  
Jianfei Zhang ◽  
Jinyang Wu ◽  
Yang Chen ◽  
Wenbin Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Critical Role ◽  
Homeobox Gene

Genetic studies have revealed a critical role of the distal-less homeobox gene 5 (Dlx5) in the pathogenesis of ovarian cancer, lung cancer, and T-cell lymphoma; however, the role and underlying mechanisms of Dlx5 in oral squamous cell carcinoma (OSCC) are largely unknown. In this study, we demonstrated that Dlx5 is up-regulated in OSCC tissues and cell lines, compared with their control groups. The results from our immunohistochemistry (IHC) analyses show that high expression levels of Dlx5 correlated with advanced TNM stages (P = 0.0001), lymph node metastasis (P = 0.0049), poor cellular differentiation (P = 0.0491), location of the tumors (P = 0.0132), and poor prognosis for the patient. We also demonstrated that knockdown of Dlx5 inhibited the viability, proliferation, and colony formation of OSCC cell lines CAL-27 and WSU-HN6 cells, probably by blocking cell cycle in the G1 phase. Furthermore, we revealed that Dlx5 exerts its biological functions via direct regulation of CCND1 in CAL-27 and WSU-HN6 cells. Ultimately, we have demonstrated that silencing of Dlx5 inhibits the growth of xenograft tumors in vivo, and that Dlx5 affects the progression of OSCC both in vitro and in vivo via directly regulating CCND1, providing a potential diagnostic biomarker and therapeutic target for OSCC.

scholarly journals Candida albicans Enhances the Progression of Oral Squamous Cell Carcinoma In Vitro and In Vivo

mBio ◽  
2022 ◽  
Author(s):  
Máté Vadovics ◽  
Jemima Ho ◽  
Nóra Igaz ◽  
Róbert Alföldi ◽  
Dávid Rakk ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Candida Albicans ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Healthy Individuals ◽  
Oral Cancer Patients

Oral squamous cell carcinoma (OSCC) is a serious health issue worldwide that accounts for 2% to 4% of all cancer cases. Previous studies have revealed a higher yeast carriage and diversity in oral cancer patients than in healthy individuals.

scholarly journals Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wen Chen ◽  
Chenzhou Wu ◽  
Yafei Chen ◽  
Yuhao Guo ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum Stress ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Ceramide Synthase

AbstractC18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

scholarly journals Effects of lentivirus-mediated shRNA targeting integrin-linked kinase on oral squamous cell carcinoma in vitro and in vivo

2015 ◽  
Vol 35 (1) ◽  
pp. 89-98 ◽  
Author(s):  
LIN QUE ◽  
DAN ZHAO ◽  
XIU-FA TANG ◽  
JI-YUAN LIU ◽  
XIANG-YU ZHANG ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Integrin Linked Kinase

scholarly journals Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

2016 ◽  
Vol 17 (3) ◽  
pp. 272 ◽  
Author(s):  
Masaaki Yasukawa ◽  
Hisako Fujihara ◽  
Hiroaki Fujimori ◽  
Koji Kawaguchi ◽  
Hiroyuki Yamada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Parp Inhibitor ◽  
Synergetic Effects

The Growth Inhibition of Targeted Pluronic/Formononetin Nanocomposite on Oral Squamous Cell Carcinoma In Vitro

2020 ◽  
Vol 12 (8) ◽  
pp. 1022-1029
Author(s):  
Ming Liu ◽  
Chen Lin ◽  
Xiaoqing Huang ◽  
Yuxiang Lin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Growth Inhibition ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laser Scanning ◽  
Critical Concentration ◽  
Laser Scanning Confocal Microscopy

Natural flavonoid formononetin (FN) has anticancer effects, but the hydrophobic structure, characteristics of the short half-life in vivo, limiting its clinical wide-ranging application. In this study, FN loaded Pluronic (PF)@folic acid (FA) micelles (FN-PF@FA), were prepared to improve the solubility, bioavailability and targeting. FA coupling PF was prepared by carbodiimide crosslinker chemical method, FN-PF@FA micelles were prepared by modified film hydration method, and compared the antitumor activity of FN loaded micelles with free FN In Vitro. The spherical smooth surface of FN-PF@FA micelles had smaller particle size (112.3±5.3 nm), high encapsulation efficiency (86.14±2.68%), high negative zeta potential (-25.8±0.57 mV), low critical concentration CMC (0.03 mg/mL), and better sustained release profile. In addition, FN-PF@FA micelles have a positive targeting effect on oral squamous cell carcinoma cells (SCC3). In 48 hours, the growth inhibition of 50% (GI50) was 28.6±1.2 μg/mL for FN and 17.4±0.78 μg/mL for FN-PF, the dose dropped by nearly 38.46%. In addition, the GI50 value of FN-PF@FA was 9.5±0.3 μg/mL, 66.43% lower than FN and 44.83% lower than FN-PF. Furthermore, the laser scanning confocal microscopy revealed that the conjugation of FA significantly improves the active targeting ability of micelles. FN-PF@FA micelles have the potential to target the release of anticancer drugs with higher bioavailability, further provides a new avenue for the application of traditional Chinese medicine extract in oral malignant tumor.

scholarly journals NF-κB-mediated lncRNA AC007271.3 promotes carcinogenesis of oral squamous cell carcinoma by regulating miR-125b-2-3p/Slug

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Ze-nan Zheng ◽  
Guang-zhao Huang ◽  
Qing-qing Wu ◽  
Heng-yu Ye ◽  
Wei-sen Zeng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Underlying Mechanisms ◽  
E Cadherin

AbstractOral squamous cell carcinoma (OSCC) is the most common oral cancer. The molecular mechanisms of this disease are not fully understood. Our previous studies confirmed that dysregulated function of long non-coding RNA (lncRNA) AC007271.3 was associated with a poor prognosis and overexpression of AC007271.3 promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. However, the underlying mechanisms of AC007271.3 dysregulation remained obscure. In this study, our investigation showed that AC007271.3 functioned as competing endogenous RNA by binding to miR-125b-2-3p and by destabilizing primary miR-125b-2, resulted in the upregulating expression of Slug, which is a direct target of miR-125b-2-3p. Slug also inhibited the expression of E-cadherin but N-cadherin, vimentin, and β-catenin had no obvious change. The expression of AC007271.3 was promoted by the canonical nuclear factor-κB (NF-κB) pathway. Taken together, these results suggested that the classical NF-κB pathway-activated AC007271.3 regulates EMT by miR-125b-2-3p/Slug/E-cadherin axis to promote the development of OSCC, implicating it as a novel potential target for therapeutic intervention in this disease.

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