M. Rezaei¹, B. Shahouzehi^2,4, S. Rahemi^1,3, 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.