Ibuprofen and diclofenac differentially affect cell viability, apoptosis and morphology changes of human cholangiocarcinoma cell lines

Abstract

Objectives: Cholangiocarcinoma is a malignant biliary epithelial duct neoplasm caused by chronic inflammation after liver fluke infection. It is amajor public health concern in the Greater Mekong sub-region in northeast Thailand. Herein, the effects of the non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and diclofenac on the cell proliferation activity of the human cholangiocarcinoma cell lines KKU-M139 and KKU-213B were studied. Methods: Cell viability was assessed with MTT assays. Inverted phase-contrast light microscopy, scanning electron microscopy and transmission electron microscopy were used to investigate the cells’ morphological alterations. Caspase 3/7 and Annexin V/PI were detected with a multimode microplate reader. Results: Ibuprofen and diclofenac decreased viability in both cell lines, and ibuprofen-treated cells exhibited reversible cell injury. In both KKU-M139 and KKU- 213B cell lines, the diclofenac-treated cells had the greatest injury. The cells exhibited features of irreversible cell injury. In addition, caspase 3/7 and Annexin V/PI detection revealed early cell apoptotic characteristics. Conclusion: These findings suggest that NSAIDs may potentially suppress cell viability. Ibuprofen and diclofenac both induced morphological changes and apoptosis.