Sangmin Kim1, Daeun You2, Yisun Jeong2, Jonghan Yu3, Seok Won Kim3, Seok Jin Nam3, Jeong Eon Lee4. 1. Department of Breast Cancer Center, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea. Electronic address: sangmin3005.kim@samsung.com. 2. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea. 3. Department of Breast Cancer Center, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea; Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea. 4. Department of Breast Cancer Center, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea; Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea. Electronic address: paojlus@hanmail.net.
Abstract
BACKGROUND: Interleukin-8 (IL-8) expression is associated with metastasis in a variety of cancer cells. PURPOSE: Here, we investigated the regulatory mechanism of IL-8 expression as well as the pharmacological effect of berberine (BBR) on IL-8 expression in triple-negative breast cancer (TNBC) cells. METHODS: The clinical value of IL-8 was analyzed by from a public database [Kaplan‑Meier plotter database. IL-8 mRNA and protein expression was analyzed by real-time PCR and ELISA, respectively. Cell invasion was analyzed by Boyden chamber assay. Tumor cell growth was analyzed by colony forming assay. RESULTS: Clinically, we observed that breast cancer patients with highly expressed IL-8 are associated with poor outcomes in areas such as relapse-free, overall, and distant metastasis-free survival. We showed that IL-8 expression is higher in TNBC cells than in non-TNBC cells. In addition, the rates of cell invasion were significantly increased by IL-8 treatment. These IL-8 levels were decreased by EGFR (Neratinib and Afatinib) and MEK (PD98059) inhibitors in TNBC cells. Finally, we observed that BBR dramatically suppresses IL-8 expression. In addition, BBR also inhibited cell invasiveness and anchorage-independent growth. Interestingly, our results showed that BBR down-regulates EGFR protein expression and dose-dependently inhibits MEK and ERK phosphorylation. CONCLUSION: Here, we demonstrate that BBR may be a promising drug to suppress cell invasiveness and growth of TNBC through IL-8-related mechanisms.
BACKGROUND:Interleukin-8 (IL-8) expression is associated with metastasis in a variety of cancer cells. PURPOSE: Here, we investigated the regulatory mechanism of IL-8 expression as well as the pharmacological effect of berberine (BBR) on IL-8 expression in triple-negative breast cancer (TNBC) cells. METHODS: The clinical value of IL-8 was analyzed by from a public database [Kaplan‑Meier plotter database. IL-8 mRNA and protein expression was analyzed by real-time PCR and ELISA, respectively. Cell invasion was analyzed by Boyden chamber assay. Tumor cell growth was analyzed by colony forming assay. RESULTS: Clinically, we observed that breast cancerpatients with highly expressed IL-8 are associated with poor outcomes in areas such as relapse-free, overall, and distant metastasis-free survival. We showed that IL-8 expression is higher in TNBC cells than in non-TNBC cells. In addition, the rates of cell invasion were significantly increased by IL-8 treatment. These IL-8 levels were decreased by EGFR (Neratinib and Afatinib) and MEK (PD98059) inhibitors in TNBC cells. Finally, we observed that BBR dramatically suppresses IL-8 expression. In addition, BBR also inhibited cell invasiveness and anchorage-independent growth. Interestingly, our results showed that BBR down-regulates EGFR protein expression and dose-dependently inhibits MEK and ERK phosphorylation. CONCLUSION: Here, we demonstrate that BBR may be a promising drug to suppress cell invasiveness and growth of TNBC through IL-8-related mechanisms.
Authors: Samia S Messeha; Najla O Zarmouh; Patricia Mendonca; Carolyn Cotton; Karam F A Soliman Journal: Mol Med Rep Date: 2020-06-15 Impact factor: 2.952