Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3681-3689. doi: 10.3892/mmr.2017.8327. Epub 2017 Dec 20.
Luteolin, a flavone, has been demonstrated to have anti‑cancer properties. In the current study, the effects of luteolin on certain carcinogenesis‑associated changes induced by pancreatitis, which are significant risk factors for pancreatic cancer, were investigated. Male six‑week‑old C57BL6 mice used in the current study were divided into three groups; the control group, acute pancreatitis group and luteolin group. Intra‑peritoneal injection of cearulein was performed in the acute pancreatitis group and luteolin group to induce acute pancreatitis whereas the luteolin group received intra‑peritoneal injection of luteolin. The control group received intra‑peritoneal injection of normal saline. Then, the expression of SOX9, phosphorylated (p‑) STAT3, p‑EGFR, cytokeratin‑19, Ki67 and N‑cadherin were determined by immunohistochemistry. Morphological changes of acinar cells were determined by hematoxylin and eosin staining. The mRNA expression of the epithelial‑mesenchymal transition markers CDH1, CDH2, Slug, Zeb1, EpCAM, ZO1, Vimentin, Snail and Twist was determined by reverse transcription‑quantitative polymerase chain reaction. It was identified that luteolin inhibits the formation of tubular complexes and ectopic expression of cytokeratin‑19 and luteolin also decreased proteins of SOX9, p‑STAT3 and p‑EGFR. In addition, luteolin inhibits proliferation and epithelial‑mesenchymal transition of acinar cells induced by acute pancreatitis. As tubular complex formation and ectopic expression of cytokeratin‑19 were two prominent characters of acinar‑ductal metaplasia, it was concluded that luteolin inhibits acinar‑ductal metaplasia induced by pancreatitis and also inhibits pancreatitis‑induced proliferation and epithelial‑mesenchymal transition of acinar cells. Acinar‑ductal metaplasia and proliferation have close associations with pancreatic carcinogenesis. It is suggested that luteolin has potential anti‑pancreatic carcinogenesis effects and merits further investigation.
木犀草素是一种类黄酮，已被证明具有抗癌特性。在本研究中，研究了木犀草素对胰腺炎引起的某些癌发生相关变化的影响，胰腺炎是胰腺癌的重要危险因素。本研究使用的雄性 6 周龄 C57BL6 小鼠分为三组：对照组、急性胰腺炎组和木犀草素组。在急性胰腺炎组和木犀草素组中进行腹腔注射 cerulein 以诱导急性胰腺炎，而木犀草素组进行腹腔注射木犀草素。对照组进行腹腔注射生理盐水。然后，通过免疫组织化学法测定 SOX9、磷酸化（p）STAT3、p-EGFR、细胞角蛋白 19、Ki67 和 N-钙黏蛋白的表达。通过苏木精和伊红染色观察腺泡细胞的形态变化。通过逆转录定量聚合酶链反应测定上皮-间充质转化标志物 CDH1、CDH2、Slug、Zeb1、EpCAM、ZO1、波形蛋白、Snail 和 Twist 的 mRNA 表达。结果表明，木犀草素抑制管状复合物的形成和细胞角蛋白 19 的异位表达，木犀草素还降低了 SOX9、p-STAT3 和 p-EGFR 的蛋白表达。此外，木犀草素抑制急性胰腺炎诱导的腺泡细胞增殖和上皮-间充质转化。由于管状复合物的形成和细胞角蛋白 19 的异位表达是腺泡-导管化生的两个突出特征，因此可以得出结论，木犀草素抑制胰腺炎诱导的腺泡-导管化生，并抑制胰腺炎诱导的腺泡细胞增殖和上皮-间充质转化。腺泡-导管化生和增殖与胰腺癌发生密切相关。提示木犀草素有潜在的抗胰腺癌发生作用，值得进一步研究。
