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Breast Cancer Research and Treatment

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02.04.2020 | Preclinical study

LLY17, a novel small molecule STAT3 inhibitor induces apoptosis and suppresses cell migration and tumor growth in triple-negative breast cancer

verfasst von: Li Pan, Xiang Chen, Shengling Fu, Wenying Yu, Chenglong Li, Tiffany Wang, Hui-Wen Lo, Jiayuh Lin

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2020

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Abstract

Purpose

Persistent STAT3 signaling is frequently detected in many cancer types including triple-negative breast cancer, and thus could potentially serve as a viable therapeutic target. We have designed a novel non-peptide compound LLY17 targeting STAT3 using Advanced Multiple Ligand Simultaneous Docking (AMLSD) methods. However, the efficacy of LLY17 has not been evaluated extensively in human and murine triple-negative breast cancer cells. In this study, we tested LLY17 in multiple human and murine triple-negative breast cancer cell lines.

Methods

Human triple-negative breast cancer MDA-MB-468, MDA-MB-231, SUM159, and BT-549 cells, and murine triple-negative breast cancer 4T1 cells were used to study the inhibition effects of LLY17. The inhibition of STAT3 activation of LLY17 was investigated using western blot analysis. Cell viability, apoptosis and migration assays were carried out by MTT assay, Caspase-3/7 assay and wound healing assay, respectively. A mammary fat pad syngeneic mouse model was used to evaluate the antitumor effect of LLY17 in vivo.

Results

LLY17 inhibited IL-6-mediated induction of STAT3 phosphorylation but had no effect on IFN-γ-induced STAT1 phosphorylation or EGF-induced ERK phosphorylation. LLY17 inhibited STAT3 phosphorylation and induced apoptosis in human and murine triple-negative breast cancer cells but exhibited minimal toxicity toward Luminal A subtype breast cancer MCF-7 cells. RNAi attenuation experiments supported the requirement of STAT3 for LLY17-mediated inhibition of cell viability in triple-negative breast cancer cells. In addition, LLY17 inhibited cell migration of human and murine triple-negative breast cancer cells. Furthermore, LLY17 suppressed tumor growth and STAT3 phosphorylation of triple-negative breast cancer cells in a mammary fat pad syngeneic mouse model in vivo.

Conclusions

Together, our findings suggest that targeting persistent STAT3 signaling by novel small molecule LLY17 may be a potential approach for the therapy of triple-negative breast cancer.

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Titel: LLY17, a novel small molecule STAT3 inhibitor induces apoptosis and suppresses cell migration and tumor growth in triple-negative breast cancer
verfasst von: Li Pan
Xiang Chen
Shengling Fu
Wenying Yu
Chenglong Li
Tiffany Wang
Hui-Wen Lo
Jiayuh Lin
Publikationsdatum: 02.04.2020
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2020
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05613-6

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

LLY17, a novel small molecule STAT3 inhibitor induces apoptosis and suppresses cell migration and tumor growth in triple-negative breast cancer

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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