黄芩苷抑制胰腺癌细胞的恶性进展及相关机制研究

Baicalin inhibits the malignant progression of pancreatic cancer cells and its related mechanisms

目的:该研究通过对黄芩苷在多种胰腺癌细胞中的治疗作用进行比较,进而探讨其对胰腺癌的体外抗肿瘤作用。方法:培养正常胰腺导管上皮细胞hTERT-HPNE和胰腺癌细胞系(PANC-1、MIA PaCa-2和BxPC-3),用不同浓度的黄芩苷(0、25、50、100、200μmol/L)处理。采用CCK-8法、Calcein AM/PI双染法和克隆形成实验检测黄芩苷对胰腺癌细胞增殖的影响;划痕实验和Transwell实验验证细胞的迁移和侵袭;流式细胞术分析检测黄芩苷对胰腺癌细胞凋亡的影响,并通过Western blot检测细胞凋亡蛋白(BCL-2、BAX、Caspase3)的表达水平。结果:黄芩苷处理各细胞后,对正常胰腺导管上皮细胞hTERT-HPNE的抑制增殖、迁移和侵袭及诱导凋亡作用不明显,而对胰腺癌细胞PANC-1、MIA PaCa-2和BxPC-3的增殖、迁移和侵袭均有不同程度的抑制作用,并可能通过上调Caspase3蛋白的表达及BAX/BCL-2的比值诱导潜在的细胞凋亡。结论:黄芩苷具有良好的生物相容性,对胰腺正常细胞毒性较低,但具有显著的抗胰腺癌特性,有望成为治疗胰腺癌的潜在药物。

Objective:To compare the therapeutic effects of baicalin on various pancreatic cancer cells to investigate its anti-tumor effects on pancreatic cancer in vitro.Methods:Human pancreatic ductal epithelial cells(hTERT-HPNE)and pancreatic cancer cell lines(PANC-1,MIA PaCa-2 and BxPC-3)were cultured and treated with different concentrations(0,25,50,100,200μmol/L)of baicalin.CCK-8 assay,Calcein AM/PI Staining and clone formation assay were performed to detect the effect of baicalin on proliferation in pancreatic cancer cells.Cell migration and invasion were assessed with wound healing assay and Transwell invasion assay.Flow cytometry analysis was performed to detect the effect of baicalin on apoptosis in pancreatic cancer cells,and Western blot analysis was performed to examine the expression of BCL-2,BAX,Caspase3.Results:Baicalin had varying degrees inhibition on the proliferation,migration,invasion and promoted apoptosis of the pancreatic cancer cells(PANC-1,MIA PaCa-2 and BxPC-3).It is also possible to induce potential apoptosis by up-regulating the protein level of Caspase3 and the ratio of BAX/BCL-2,while has no obvious effect on pancreatic ductal epithelial cells(hTERT-HPNE).Conclusion:Our work demonstrated that baicalin exhibited good biological safety and low toxicity to normal pancreatic cell,but it has significant anti-cancer properties and is expected to be a potential drug for the treatment of pancreatic cancer.