Human Placenta-derived Mesenchymal Stem Cells Inhibit Proliferation and Promote Apoptosis in Cholangiocarcinoma Cell Lines via Suppressing JAK2/STAT3 Signaling

Abstract

Introduction: Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the bile duct. Incidence and mortality increase worldwide because of late diagnosis and a lack of therapeutic options. Mesenchymal stem cells (MSC) can secrete several cytokines to promote or inhibit the progression of many cancer cell types. However, the effect of human placenta-derived MSCs (PL-MSC) on CCA progression has not been clarified.

Objectives: The present study aims to investigate the effects and molecular mechanisms of conditioned media derived from PL-MSC (PL-CM) on three CCA cell lines (KKU100, KKU213A, and KKU213B).

Methods: CCA cells were cultured with PL-CM to examine cell proliferation and apoptosis by MTT assay and annexin V/PI analysis, respectively. JC-1 staining, caspase 3 activity, and western blot were used to investigate the mechanism of PL-CM induced apoptosis of CCA cell lines through mitochondrial apoptotic pathway and JAK2/STAT3 signaling.

Results: PL-CM could suppress proliferation and promote apoptosis of all CCA cell lines by inducing mitochondrial apoptotic pathways, most likely through suppression of the JAK2/ STAT3 signaling pathway.

Conclusions: This study suggests PL-CM has a potent anti-cancer effect on CCA cells. Therefore, PL-MSC may provide a basis for further clinical trials to study as well as a possible alternative treatment for CCA patients.