Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
BMC Vet Res. 2012 Dec 17;8:244. doi: 10.1186/1746-6148-8-244.
STAT3 [1] has been shown to be dysregulated in nearly every major cancer, including osteosarcoma (OS). Constitutive activation of STAT3, via aberrant phosphorylation, leads to proliferation, cell survival and resistance to apoptosis. The present study sought to characterize the biologic activity of a novel allosteric STAT3 inhibitor, LLL12, in canine OS cell lines.
We evaluated the effects of LLL12 treatment on 4 canine OS cell lines and found that LLL12 inhibited proliferation, induced apoptosis, reduced STAT3 phosphorylation, and decreased the expression of several transcriptional targets of STAT3 in these cells. Lastly, LLL12 exhibited synergistic anti-proliferative activity with the chemotherapeutic doxorubicin in the OS lines.
LLL12 exhibits biologic activity against canine OS cell lines through inhibition of STAT3 related cellular functions supporting its potential use as a novel therapy for OS.
STAT3[1]在几乎所有主要癌症中都存在失调，包括骨肉瘤（OS）。STAT3 的组成性激活，通过异常磷酸化，导致增殖、细胞存活和抗凋亡。本研究旨在表征新型变构 STAT3 抑制剂 LLL12 在犬骨肉瘤细胞系中的生物学活性。
我们评估了 LLL12 治疗对 4 种犬骨肉瘤细胞系的影响，发现 LLL12 抑制增殖，诱导细胞凋亡，降低 STAT3 磷酸化，并降低这些细胞中 STAT3 的几个转录靶标表达。最后，LLL12 与 OS 系中的化疗药物多柔比星表现出协同的抗增殖活性。
LLL12 通过抑制 STAT3 相关细胞功能对犬骨肉瘤细胞系表现出生物学活性，支持其作为骨肉瘤新型治疗方法的潜在用途。
