• Journal of Ginseng Research
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• 제45권5호
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• pp.610-616
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• 2021

Background: Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood. Methods: We investigated antiinflammatory effects of Rg3 on an in vitro model using HMC-1 cells stimulated by PMA plus calcium ionophore (PMACI), as well as an in vivo model using PMA-induced mouse ear edema. TSLP and vascular endothelial growth factor (VEGF) levels were detected using enzyme-linked immunosorbent assay or real-time PCR analysis. Murine double minute 2 (MDM2) and hypoxia-inducible factor 1α (HIF1α) expression levels were detected using Western blot analysis. Results: Rg3 treatment restrained the production and mRNA expression levels of TSLP and VEGF in activated HMC-1 cells. Rg3 down-regulated the MDM2 expression level increased by PMACI stimulation. The HIF1α expression level was also reduced by Rg3 in activated HMC-1 cells. In addition, Rg3-administered mice showed the decreased redness and ear thickness in PMA-irritated ear edema. Rg3 inhibited the TSLP and VEGF levels in the serum and ear tissue homogenate. Moreover, the MDM2 and HIF1α expression levels in the ear tissue homogenate were suppressed by Rg3. Conclusion: Taken together, the current study identifies new mechanistic evidence about MDM2/HIF1α pathway in the antiinflammatory effect of Rg3, providing a new effective therapeutic strategy for the treatment of skin inflammatory diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.4057-4060
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• 2015

Cigarette smoke contains oxidants and free radicals which are carcinogens that can induce mutations in humans. Single nucleotide polymorphisms (SNPs) are the most frequent genetic alterations found in the human genome. In the present study, we have examined the ability of the murine double minute 2 (Mdm2) (rs769412) A>G polymorphism in cigarette smokers to predict risk of cancers. Our results showed that of smokers, 87% were found with AA genotype, 10% with heterozygous AG genotype, and 3% with GG genotype. The heterozygous AG genotype was observed in a lower percentage of smokers (10%) as compared to non-smokers (18%), whereas, homozygous AA genotype was observed in lower percentage of non-smokers (81%) as compared to the smokers (87%). The results from present study support the association with an allele and AG genotype in non-smokers. However, further studies are required to establish the role of Mdm2 (rs769412) C>T in cigarettes smokers and diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3295-3300
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• 2016

Background: Different types of cancer exhibit abnormalities in cell cycle regulators. The murine double minute-2(MDM2) cell cycle regulator is a proto-oncogene that negatively regulates the P53 tumour suppressor gene. Surface epithelial tumours constitute approximately two thirds of ovarian neoplasms. Each histologic type can be classified as benign, borderline and malignant. This study aimed to examine immunohistochemical expression of the MDM2 protein in ovarian serous and mucinous epithelial tumours (benign, borderline and malignant). Materials and Methods: This study included forty five ovarian tumours, subdivided into fifteen cystadenomas (5 serous and 10 mucinous), fifteen borderline tumours (11 serous and 4 mucinous) and fifteen cystadenocarcinomas (9 serous and 6 mucinous). Paraffin sections were stained with haematoxylin and eosin for histopathologic study, and with mouse monoclonal anti-MDM2 antibody for immunohistochemistry. Results: MDM2 positivity was detected in 28.9% of the studied ovarian tumours. All benign tumours were negative and positivity was significantly higher in malignant than borderline tumours (P value of chi-square test =0.000). Significantly, all MDM2 positive mucinous tumours were malignant with no positive mucinous borderline tumours. Malignant tumours showed positive MDM2 expression in 83.3% of mucinous type and in 55.6% of serous type. Borderline serous tumours showed negative MDM2 in 72.7% of cases (P value of Z test =0.04). Conclusions: Alterations in the expression of the cell cycle regulator (MDM2) occur early in the process of tumourigenesis in serous and mucinous ovarian tumours. We suggest that MDM2 may be used in those tumours as a marker for risk stratification and identification of cases with cancer development and progression. We recommend further studies on MDM2 immunohistochemistry, in conjunction with adjuvant methods as DNA ploidy and FISH gene amplification, focusing on the mucinous tumours and differentiating between the three tumour categories, benign, borderline and malignant.