Centre for Regenerative Medicine, Department of Biology & Biochemistry, University of Bath, Bath, UK.
Cell Oncol (Dordr). 2013 Jul;36(4):289-301. doi: 10.1007/s13402-013-0134-8. Epub 2013 May 16.
Previous research has suggested a putative utility of pancreatic (pro)enzymes in cancer treatment. The aim of the present study was to investigate the in vitro effects of a mixture of two pancreatic pro-enzymes, i.e., Chymotrypsinogen and Trypsinogen, and the enzyme Amylase on three human cancer cell lines, i.e., OE33 (derived from an oesophageal carcinoma), Panc1 (derived from a pancreatic carcinoma) and Caco-2 (derived from a colon carcinoma).
After treatment of the three cancer cell lines with different doses of the (pro)enzymes for up to 7 days, we observed (i) growth inhibition in a dose-dependent manner, (ii) enhanced expression of β-catenin and E-cadherin and decreased expression of several epithelial-mesenchymal transition (EMT)-associated genes, such as Vimentin, Snail and Slug, (iii) differentiation of Caco-2 cells, including the appearance of cell-specific differentiated structures such as microvilli and tight junctions, the acquisition of a more regular polygonal morphology, and an increased expression of the intestinal differentiation markers alkaline phosphatase and cytokeratin 8, and (iv) differentiation of Panc1 cells, including the formation of cell aggregates, an increment on lamellar bodies and an increased expression of the pancreatic differentiation markers glucagon and insulin.
Our results show that the treatment of three different human cancer cell lines with pancreatic (pro)enzymes results in an enhancement of cell adhesion, an attenuation of several EMT-associated markers, and an increase in the expression of several differentiation-associated markers, suggesting the acquisition of a less malignant phenotype and a decrease in proliferative capacity due to lineage-specific cellular differentiation.
先前的研究表明胰腺（前）酶在癌症治疗中具有潜在的效用。本研究的目的是研究两种胰腺前酶，即糜蛋白酶原和胰蛋白酶原，以及酶淀粉酶对三种人癌细胞系，即 OE33（来源于食管癌）、Panc1（来源于胰腺癌）和 Caco-2（来源于结肠癌）的体外影响。
在用不同剂量的（前）酶处理三种癌细胞系长达 7 天之后，我们观察到（i）以剂量依赖性方式抑制生长，（ii）β-连环蛋白和 E-钙黏蛋白的表达增强，以及几个上皮-间充质转化（EMT）相关基因，如波形蛋白、Snail 和 Slug 的表达降低，（iii）Caco-2 细胞的分化，包括出现细胞特异性分化结构，如微绒毛和紧密连接，获得更规则的多边形形态，以及肠分化标记物碱性磷酸酶和细胞角蛋白 8 的表达增加，以及（iv）Panc1 细胞的分化，包括细胞聚集的形成、板层小体的增加以及胰腺分化标记物胰高血糖素和胰岛素的表达增加。
我们的结果表明，用胰腺（前）酶处理三种不同的人癌细胞系可增强细胞黏附，减弱几个 EMT 相关标志物的表达，并增加几个分化相关标志物的表达，提示获得较少恶性表型和增殖能力下降，这是由于谱系特异性细胞分化。
