JSI124 inhibits breast cancer cell growth by suppressing the function of B cells via the downregulation of signal transducer and activator of transcription 3

Ren,Yi; Yu,Kun; Sun,Su'an; Li,Zhi; Yuan,Jin; Han,Xue  Dong; Shi,Jianhua; Zhen,Linlin

doi:10.3892/ol.2014.2221

JSI124 inhibits breast cancer cell growth by suppressing the function of B cells via the downregulation of signal transducer and activator of transcription 3

Authors:
- Yi Ren
- Kun Yu
- Su'an Sun
- Zhi Li
- Jin Yuan
- Xue Dong Han
- Jianhua Shi
- Linlin Zhen
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Affiliations: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China, Department of Cardiology, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China, Department of Pathology, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China
Published online on: June 4, 2014 https://doi.org/10.3892/ol.2014.2221
Pages: 928-932

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Abstract

JSI‑124, also known as cucurbitacin I, is a selective inhibitor of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and in vitro and in vivo studies have found that it has anti‑tumor and anti‑proliferative properties. However, the role of JSI124 in tumor‑associated B cells has yet to be elucidated. The present study demonstrated that STAT3 is significantly activated in the B cells of patients with breast cancer. Furthermore, a 4T1 tumor‑bearing mouse model revealed that JSI124 effectively inhibited tumor growth. Moreover, the STAT3 levels in the B cells of the JSI124‑treated mice were found to be significantly decreased. B cells from normal Balb/c mice, the 4T1‑bearing mice and the JSI124‑treated 4T1 mice were purified and intravenously injected into the 4T1‑bearing Balb/c mice. Tumor growth data showed that the 4T1 tumor mouse‑derived B cells, which exhibited a higher level of STAT3, promoted tumor growth, while the JSI124‑treated 4T1 mouse‑derived B cells had a tumor suppressor function. Furthermore, the B cells from the normal Balb/c mice were treated with phosphate‑buffered saline, JSI124 and 4T1 tumor cells, then the B cell STAT3 levels were analyzed. Following injection into the 4T1 mice, the 4T1 cell‑treated B cells were observed to enhance tumor growth, while the JSI124‑treated B cells were found to inhibit the growth of 4T1 tumors in vivo. These findings show a novel role of JSI124 in tumor suppression through the downregulation of the expression of STAT3 in tumor‑associated B cells.

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