Tag Archives: methotrexate

Effect of IRAK1/4 inhibitor on IL-1β, IL-6, INF-γ and TNF-α expression in breast cancer cells of several lines

M. Rezaei1, B. Shahouzehi2,4, S. Rahemi1,3, H. Fallah1*, M. Salarkarimi1

1Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
2Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
3Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
4Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
*e-mail: hf59ma@gmail.com

Received: 28 July 2020; Accepted: 07 July 2021

Recent studies have shown that inflammation mediated via interleukin-1 receptor-associated kinases (IRAKs) is associated with cancer cells drug resistance. We aimed to evaluate the expression of inflammatory cytokines as the potential mechanism involved in the development of cancer cells resistance to conventional chemotherapy drugs. Breast cancer cells of BT549, BT20 and MB468 lines were treated with IRAK 1/4 inhibitor alone or in combination with chemotherapeutic agents methotrexate and topotecan. Expression of IL-1β, IL-6, TNF-α, and IFN-γ genes was quantified by real-time PCR. It was found that IRAK1/4 inhibitor suppressed IL-1β expression in BT549 cells at most and had minimal effect on IL-6 expression in MB468 cells. For the first time we showed that concomitant use of IRAK1/4 inhibitor with topotecan and methotrexate reduced IL-1β, IFN γ, TNF-α and IL-6 expression in BT-20, BT-549, MB-468 cell lines compared to the controls. It is suggested that specific IRAK inhibitors in combination with conventional chemotherapy can be used in cancer treatment to increase drug sensitivity and decrease the risk of tumor recurrence.

Methotrexate effect on biochemical indices of psoriasis patients depends on MTHFR gene polymorphism

O. M. Fedota1, L. V. Roschenyuk2,3, T. V. Tyzhnenko1,
N. G. Puzik1,3, V. M. Vorontsov1, P. P. Ryzhko1

1V.N. Karazin Kharkiv National University, Ukraine;
2Kharkiv Regional Clinical Skin and Venereal Diseases Dispensary №1, Ukraine;
3Kharkiv National Medical University, Ukraine;
e-mail: tyzhnenko@ukr.net

Received: 13 June 2019; Accepted: 29 November 2019

Methotrexate (MTX) is the immunosuppressive anti-inflammatory drug and the antagonist of the enzyme dihydrofolate reductase. Pharmacogenomic studies and clinical evidences suggest that altered response to MTX  in patients with different diseases is associated with polymorphisms of genes that regulate folate metabolism. The purpose of the article was to analyze the methotrexate effect on the biochemical indices of psoriasis patients depending on methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms. Effects of two single-nucleotide polymorphisms, C677T and A1298C, were studied. An increase of alanine aminotransferase and aspartate aminotransferase activity above the normal level in the patients with both MTHFR gene polymorphisms after methotrexate intake was observed. In patients with CC, TT, CT genotypes for C677T polymorphism and AA genotype for A1298C polymorphism of MTHFR gene, significant differen­ces in alpha-amylase activity before and after treatment with methotrexate were detected. Analysis of the biochemical indices of  patients with arthropathic and vulgaris psoriasis showed that the positive effect of MTX treatment could be associated with wild-type alleles in both  polymorphisms of MTHFR gene, while the ineffectiveness of methotrexate was associated with the dihеterozygous genotype. The largest number of smokers was found within the CTAA genotype group (37.5%), while no smokers were observed within TTAA patients and most of CCAA patients. The data obtained testify the utility of the individual approach to the psoriasis patients therapy taking into account genetic background.