Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Department of Digestive Tumor Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Med Sci Monit. 2019 Apr 21;25:2943-2949. doi: 10.12659/MSM.914244.
BACKGROUND Pancreatic cancer is a major cause of mortality worldwide. Inefficient drugs, their adverse effects, and the development of drug resistance make it difficult to curb the growing incidence of pancreatic cancer. Against this backdrop, the development new drug regimens with no or negligible adverse effects is imperative. We assessed the anticancer effects of a plant-derived sesquiterpene - matricine - against capan-2 pancreatic cancer cells. MATERIAL AND METHODS Cell viability was determined by MTT assay. AO/EB, DAPI, and annexin V/PI staining were used to detect apoptosis. Transwell assays were used for monitoring of cell migration and invasion. Immunoblotting was used to examine the expression of proteins. RESULTS The results showed that matricine halted the proliferation of capan-2 cells, with minimal toxic effects on normal pancreatic cells. The anticancer effects were due to the induction of apoptotic cell death, which was allied with activation of caspases 3 and 9, upregulation of Bax, and downregulation of Bcl-2. Moreover, matricine suppressed the migration and invasive abilities of pancreatic cancer cells at IC50. We also assessed the effects of matricine on the mTOR/PI3K/AKT signalling pathway. We found that matricine efficiently blocked this pathway, suggesting the anticancer potential of matricine. CONCLUSIONS Matricine induced antiproliferative effects in capan-2 human pancreatic cancer cells through inducing apoptosis, caspase activation, inhibition of cell migration and invasion, and blocking the mTOR/PI3K/AKT signalling pathway.
胰腺癌是全球主要的致死病因之一。低效药物、药物的不良反应以及耐药性的发展，使得控制胰腺癌发病率的上升变得困难重重。在此背景下，开发无不良反应或不良反应极小的新药物方案势在必行。我们评估了一种植物源倍半萜 - 千里光宁 - 对 Capan-2 胰腺癌细胞的抗癌作用。材料和方法：通过 MTT 测定法测定细胞活力。使用 AO/EB、DAPI 和 Annexin V/PI 染色检测细胞凋亡。通过 Transwell 测定法监测细胞迁移和侵袭。通过免疫印迹检测蛋白表达。结果：结果表明，千里光宁抑制了 Capan-2 细胞的增殖，对正常胰腺细胞的毒性作用最小。抗癌作用是由于诱导细胞凋亡所致，这与 caspase-3 和 caspase-9 的激活、Bax 的上调和 Bcl-2 的下调有关。此外，千里光宁以 IC50 抑制了胰腺癌细胞的迁移和侵袭能力。我们还评估了千里光宁对 mTOR/PI3K/AKT 信号通路的影响。我们发现千里光宁能有效地阻断该通路，表明千里光宁具有抗癌潜力。结论：千里光宁通过诱导细胞凋亡、激活半胱天冬酶、抑制细胞迁移和侵袭以及阻断 mTOR/PI3K/AKT 信号通路，对 Capan-2 人胰腺癌细胞发挥抗增殖作用。
