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

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.