title: 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), andin vitroandin vivostudies 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 tumorsin 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.
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Cardiology, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Pathology, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China.
authors.forename: Su'an
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiology, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China.
authors.forename: Xue Dong
authors.initials: XD
authors.lastname: Han
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, P.R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhen
keywords: 4T1 tumor; B cells; JSI124; signal transducer and activator of transcription 3