Dynamic changes in the gene expression profile during rat oral carcinogenesis induced by 4-nitroquinoline 1-oxide

Ge, Shuyun; Zhang, Ji; Du, Yanzhi; Zhou, Zengtong; Lou, Jianing

doi:10.3892/mmr.2016.4883

Cited by 5 publications

(5 citation statements)

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“…Gene expression of the pro-inflammatory biomarkers Cxcl1, Mif , and Nfe2l2 were downregulated in carcinogen-induced rats fed with 5 or 10% BRB diet (Figure 4 A). These genes have been shown to play a role in oral carcinogenesis in preclinical models as well as in human oral cancer ( 26 , 27 ). Prostaglandin-endoperoxidase synthase, a key enzyme in prostaglandin biosynthesis, is especially critical in mediating the pathologic consequences of chronic inflammation in OSCC ( 23 ).…”

Section: Resultsmentioning

confidence: 99%

“…Evidence for inhibition of proliferative signaling as a mechanism of BRB-mediated chemoprevention of oral cancer is demonstrated by the downregulation of cell cycle associated genes that are typically associated with oral carcinogenesis: Aurka, Ccna1, Ccna2 , and Ccnd1 ( 15 , 27 ). This is further supported by the reduction in the expression of the proliferative marker Ki-67 in BRB-treated, carcinogen-induced rats.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Pro-inflammatory and Anti-apoptotic Biomarkers during Experimental Oral Cancer Chemoprevention by Dietary Black Raspberries

et al. 2017

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Oral cancer continues to be a significant public health problem worldwide. Recently conducted clinical trials demonstrate the ability of black raspberries (BRBs) to modulate biomarkers of molecular efficacy that supports a chemopreventive strategy against oral cancer. However, it is essential that a preclinical animal model of black raspberry (BRB) chemoprevention which recapitulates human oral carcinogenesis be developed, so that we can validate biomarkers and evaluate potential mechanisms of action. We therefore established the ability of BRBs to inhibit oral lesion formation in a carcinogen-induced rat oral cancer model and examined potential mechanisms. F344 rats were administered 4-nitroquinoline 1-oxide (4NQO) (20 µg/ml) in drinking water for 14 weeks followed by regular drinking water for 6 weeks. At week 14, rats were fed a diet containing either 5 or 10% BRB, or 0.4% ellagic acid (EA), a BRB phytochemical. Dietary administration of 5 and 10% BRB reduced oral lesion incidence and multiplicity by 39.3 and 28.6%, respectively. Histopathological analyses demonstrate the ability of BRBs and, to a lesser extent EA, to inhibit the progression of oral cancer. Oral lesion inhibition by BRBs was associated with a reduction in the mRNA expression of pro-inflammatory biomarkers Cxcl1, Mif, and Nfe2l2 as well as the anti-apoptotic and cell cycle associated markers Birc5, Aurka, Ccna1, and Ccna2. Cellular proliferation (Ki-67 staining) in tongue lesions was inhibited by BRBs and EA. Our study demonstrates that, in the rat 4NQO oral cancer model, dietary administration of BRBs inhibits oral carcinogenesis via inhibition of pro-inflammatory and anti-apoptotic pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of Pro-inflammatory and Anti-apoptotic Biomarkers during Experimental Oral Cancer Chemoprevention by Dietary Black Raspberries

et al. 2017

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“…17 However, in this study, the different degrees of dysplasia in each treatment group can be due to gene variations resulting in cell changes in a single group. According to Ge et al (2016), 18 approximately 600 genes influence the process of normal cell changes culminating in malignancy, including transcription factors, oncogenes, differentiation markers, tumour suppressors, and metastatic proteins.…”

Section: Discussionmentioning

confidence: 99%

The correlation between exposure to cigarette smoke and the degree of mucosal epithelium-based dysplasia in Rattus norvegicus tongues

Prijaryanti¹,

Ernawati²,

Radithia³

et al. 2019

Dent. J.

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Background: Cigarette smoke contains various carcinogenic substances such as polycyclic aromatic hydrocarbons and nitrosamines. These chemicals not only have the potential to damage DNA, but can also induce genetic mutations and activate genes that function during apoptosis. Thus, if the gene is dysregulated, it will cause cells to survive, proliferate and subsequently lead to the development of cancerous ones. Histologically, the carcinogenic process affecting the oral cavity starts with hyperplasia and dysplasia, followed by severe dysplasia then leading to invasive cancer and metastatic processes in other bodies. Purpose: This study aims to reveal the correlation between exposure to cigarette smoke and the degree of epithelial dysplasia evident in research subjects. Methods: This study used 27 samples of Rattus norvegicus tongue, divided into three groups, namely; a control group, a treatment group subjected to four weeks’ exposure to cigarette smoke, and a treatment group subjected to exposure lasting eight weeks. Each rat was placed in an individual chamber and exposed to smoke from 20 cigarettes introduced by a pump via a pipe for 7.5 minutes. The degree of epithelial dysplasia in each case was subsequently observed microscopically using HE staining technique. Results: Mild epithelial dysplasia increased by 0.82%, during the fourth week of exposure to cigarette smoke and by 2.99% during the eighth week. Similarly, moderate epithelial dysplasia rose by 5.29% during the fourth week of exposure and 5.99% during the eighth week. Severe epithelial dysplasia also increased by 2.2% during the fourth week of exposure and by 2.66% during the eighth week. Conclusion: The longer the exposure to cigarette smoke, the higher the degree of ensuing dysplasia.

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“…Expression levels of CoTI and JAK3 were evaluated using an evergreen based technique, and GAPDH was used as the endogenous control. Primers for the estimation of CoTI were: forward primer 5 -ATCAGCCCAAACCCCAAGGAGA-3 and reverse primer 5 -CGCAGGAAGGTCAGCTG GATAG-3 , primers for the determination of JAK 3 were: JAK3 F 5 -CCTGGAGTGGCACGA GAATC-3 , JAK3 R 5 -TCCACAACCTCCCGCCTAT-3 [46], while primers used for GAPDH estimation were: forward primer 5 -CCATTCTTCCACCTTTGATGCT-3 and reverse primer 5 -TGTTGCTGTAGCCATATTCATTGT-3 [47]. Denaturation was carried out for 10 min at 95 • C, after which a two-step cycling technique was used for 40 cycles: denaturation for 30 s at 95 • C, followed by annealing and extension for 30 s at 60 • C. RT-PCR results were analyzed using the comparative cycle threshold method (2 −∆∆Ct method [48]) and represented a fold-change in expression compared to the untreated control group.…”

Section: Coti and Jak3 Rna Isolation And Real-time Pcr (Rt-pcr) Inves...mentioning

confidence: 99%

Characterization and Bio-Evaluation of the Synergistic Effect of Simvastatin and Folic Acid as Wound Dressings on the Healing Process

Hashem,

Alotaibi,

Elsayed

et al. 2023

Pharmaceutics

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Wound healing is a significant healthcare problem that decreases the patient’s quality of life. Hence, several agents and approaches have been widely used to help accelerate wound healing. The challenge is to search for a topical delivery system that could supply long-acting effects, accurate doses, and rapid healing activity. Topical forms of simvastatin (SMV) are beneficial in wound care. This study aimed to develop a novel topical chitosan-based platform of SMV with folic acid (FA) for wound healing. Moreover, the synergistic effect of combinations was determined in an excisional wound model in rats. The prepared SMV-FA-loaded films (SMV-FAPFs) were examined for their physicochemical characterizations and morphology. Box-Behnken Design and response surface methodology were used to evaluate the tensile strength and release characteristics of the prepared SMV-FAPFs. Additionally, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction pattern (XRD), and animal studies were also investigated. The developed SMV-FAPFs showed a contraction of up to 80% decrease in the wound size after ten days. The results of the quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant upregulation of dermal collagen type I (CoTI) expression and downregulation of the inflammatory JAK3 expression in wounds treated with SMV-FAPFs when compared to control samples and individual drug treatments. In summary, it can be concluded that the utilization of SMV-FAPFs holds great potential for facilitating efficient and expeditious wound healing, hence presenting a feasible substitute for conventional topical administration methods.

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Dynamic changes in the gene expression profile during rat oral carcinogenesis induced by 4-nitroquinoline 1-oxide

Cited by 5 publications

References 48 publications

Inhibition of Pro-inflammatory and Anti-apoptotic Biomarkers during Experimental Oral Cancer Chemoprevention by Dietary Black Raspberries

Inhibition of Pro-inflammatory and Anti-apoptotic Biomarkers during Experimental Oral Cancer Chemoprevention by Dietary Black Raspberries

The correlation between exposure to cigarette smoke and the degree of mucosal epithelium-based dysplasia in Rattus norvegicus tongues

Characterization and Bio-Evaluation of the Synergistic Effect of Simvastatin and Folic Acid as Wound Dressings on the Healing Process

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