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2'-Hydroxyflavanone inhibits the progression of pancreatic cancer cells and sensitizes the chemosensitivity of EGFR inhibitors via repressing STAT3 signaling.
Cancer Letters ( IF 9.1 ) Pub Date : 2019-12-04 , DOI: 10.1016/j.canlet.2019.11.041
Yangyang Yue 1 , Weikun Qian 1 , Jie Li 1 , Shiqi Wu 2 , Mengzhao Zhang 2 , Zheng Wu 1 , Qingyong Ma 1 , Zheng Wang 1
Affiliation  

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, and chemotherapy is still an important treatment. It is urgent to develop new medicines because of the limitation and side effects of chemotherapy. 2'-Hydroxyflavanone (2HF) is a citrus-bioflavonoid that is considered to have anti-cancer efficacy. Compared to human pancreatic ductal epithelial cells hTERT-HPNE, more significant growth-inhibitory effects were seen in PDAC cells BxPC-3 and MIA PaCa-2. We showed that apoptosis was induced and that the cell cycle was arrested when cells were treated with 2HF. The expression of the molecular proteins cleaved PARP, cleaved Caspase3, Bax, Bcl-2, CyclinD1, and p27 changed correspondingly. Also, we observed anti-metastatic effects and changes in MMP9, E-cadherin, N-cadherin and Vimentin when cells were treated with a low dose of 2HF. Suppression of STAT3 and EGFR phosphorylation was also identified as a result of treatment with a combination of 2HF and EGFR inhibitors. The in vivo antitumor effects in KPC mice were consistent with those observed in vitro. 2HF has impactful anti-cancer efficacy and sensitizes human pancreatic cancer cells to EGFR inhibitors through the inhibition of STAT3.

中文翻译:


2'-Hydroxyflavanone 可抑制胰腺癌细胞的进展,并通过抑制 STAT3 信号传导来提高 EGFR 抑制剂的化疗敏感性。



胰腺导管腺癌(PDAC)是最致命的恶性肿瘤之一,化疗仍然是重要的治疗方法。由于化疗的局限性和副作用,迫切需要开发新药。 2'-羟基黄烷酮 (2HF) 是一种柑橘生物类黄酮,被认为具有抗癌功效。与人胰腺导管上皮细胞hTERT-HPNE相比,PDAC细胞BxPC-3和MIA PaCa-2具有更显着的生长抑制作用。我们发现,当细胞用 2HF 处理时,细胞凋亡被诱导,细胞周期被抑制。 cleaved PARP、cleaved Caspase3、Bax、Bcl-2、CyclinD1、p27等分子蛋白表达量发生相应变化。此外,我们还观察到用低剂量 2HF 处理细胞时的抗转移作用以及 MMP9、E-钙粘蛋白、N-钙粘蛋白和波形蛋白的变化。 2HF 和 EGFR 抑制剂联合治疗也可抑制 STAT3 和 EGFR 磷酸化。 KPC小鼠的体内抗肿瘤作用与体外观察到的一致。 2HF 具有显着的抗癌功效,并通过抑制 STAT3 使人胰腺癌细胞对 EGFR 抑制剂敏感。
更新日期:2019-12-04
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