Induction of Cell Death and Apoptosis of Oroxylum Indicum Extract With Gemcitabine On Human Cholangiocarcinoma Cells Through Reducing Epidermal Growth Factor Receptor

Background: Cholangiocarcinoma (CCA), epithelial bile duct cancer, is deadly cancer with a very poor prognosis and standard anticancer drugs strategy remains poor and unfavorable outcomes. Objectives: In this study, we examined how Oroxylum indicum leaf extract in combination with gemcitabine (anticancer drug) affects the viability, apoptosis, and migration of CCA cells. Materials and Methods: Two CCA cells, KKU‑100 and KKU‑M452, were incubated with O. indicum or gemcitabine or in combination for 24‑72 hr and these effects were explored by using the sulforhodamine B, colony formation, cell cycle arrest, ROS formation, mitochondrial function, migration, and Western blot analysis. Results: O. indicum expressively suppressed the growth of both CCA cells at 72 hr with IC50 values were 9.88 ± 1.36 and 8.56 ± 1.02 µg/mL for KKU‑100 and KKU‑M452 cells, with the number of cells were decreased by dose‑dependent manner. Further, the extract caused the reduction of colony formation and then suppressed the cells at G0/G1 phase for KKU‑100 and S to G2/M phase for KKU‑M452 cells. At 250 µg/mL, two CCA cells generated ROS formation along with decreasing mitochondrial function and then led to induce cancer cells apoptosis. Furthermore, O. indicum extract inhibited CCA cell migration via decreasing MMP‑9 expression levels. The mechanism of its action was significant suppressed EGFR and caspase 3 levels. Combination group of O. indicum plus gemcitabine found that O. indicum potentiated gemcitabine to inhibit cell viability, induce apoptosis, increase ROS formation, decrease mitochondrial function, and suppress EGFR expression. Conclusion: O. indicum leaf extracts with potentiation of gemcitabine can reduce CCA cell growth, induce apoptosis, and cell migration through decreasing EGFR and caspase 3 expression. O. indicum could be useful for enhancing the activity of anticancer drugs displayed to prevent or treat CCA.