Expression and Prognostic Implication of the Nuclear Receptors Farnesoid X Receptor and Pregnane X Receptor in Human Cholangiocarcinoma.

Background/aim: Cumulative evidence reveals the contribution of nuclear receptors in the development and progression of cancers. The present study aimed to investigate the expression of two nuclear receptors, farnesoid X receptor (FXR) and pregnane X receptor (PXR), in cholangiocarcinoma (CCA) tissues and the correlation of their expression with clinicopathological features.

Materials And Methods: FXR and PXR expression was evaluated in 111 resected CCA patient samples using immunohistochemistry, and the association of its expression with clinicopathological parameters was analyzed.

Synergistic suppression of cholangiocarcinoma cells via DNA damage response and cell cycle arrest by dual targeting PARP and ATM in DNA damage repair pathway.

This study investigated alterations in DNA damage repair (DDR) genes in cholangiocarcinoma (CCA) influencing cellular vulnerability to DDR inhibitors, notably poly (ADP-ribose) polymerase inhibitors (PARPi) and ataxia-telangiectasia mutated inhibitors (ATMi). Genomic DDR alterations in CCA tumors were identified via cBioPortal. The cytotoxic effect of the inhibitors was determined in 8 CCA cell lines.

Establishment and genomic profiling of cholangiocarcinoma cells with functional characterization.

Cholangiocarcinoma (CCA) is a highly lethal hepatobiliary malignancy, with prognosis is influenced by anatomical subtypes and etiological factors. This study successfully established three CCA cell lines: KKU-097, KKU-466, and KKU-610, from the primary tumors of patients in liver fluke-endemic areas. These cells represent the perihilar CCA (pCCA) and intrahepatic CCA (iCCA) subtypes.

Network pharmacology- and cell-based assessments identify the FAK/Src pathway as a molecular target for the antimetastatic effect of momordin Ic against cholangiocarcinoma.

Previous studies have indicated the efficacy of momordin Ic (MIc), a plant-derived triterpenoid, against several types of cancers, implying its potential for further development. However, comprehensive insights into the molecular mechanisms and targets of MIc in cholangiocarcinoma (CCA) are lacking. This study aimed to investigate the actions of MIc against CCA at the molecular level.

Dual blockage of PI3K-mTOR and FGFR induced autophagic cell death in cholangiocarcinoma cells.

Purpose: To assess the impact of concurrent inhibition of the FGFR and PI3K/mTOR signaling pathways on oncogenic characteristics in cholangiocarcinoma (CCA) cells, including proliferation, autophagy, and cell death.

Materials And Methods: KKU-213A, KKU-100, and KKU-213C cells were treated with either infigratinib or PKI-402 alone or in combination. Cell viability and cell death were evaluated using the sulforhodamine B (SRB) assay and acridine orange/ethidium bromide (AO/EB) staining.

FGF10/FGFR2 Signaling: Therapeutically Targetable Vulnerability in Ligand-responsive Cholangiocarcinoma Cells.

Background/aim: Increasing evidence has revealed FGFR2 as an attractive therapeutic target for cancer including cholangiocarcinoma (CCA). The present study investigated the oncogenic mechanisms by which FGF10 ligand activates FGFR2 in CCA cells and determined whether FGFR inhibitors could suppress FGF10-mediated migration of CCA cells.

Materials And Methods: Effects of FGF10 on the proliferation, migration, and invasion of KKU-M213A cells were assessed using clonogenic and transwell assays.

Leaf Extract Alleviates Dyslipidemia and Hepatic Steatosis by Modifying the Expression of Lipid Metabolism-Related Genes in Rats Fed a High Fat-High Fructose Diet.

This study evaluated the effect of leaf extract (PIE) on dyslipidemia and lipid accumulation in the liver, emphasizing its molecular mechanisms in regulating lipid metabolism in rats fed a high fat-high fructose diet (HFFD). Male rats were fed HFFD (40% lard and 20% fructose) for ten weeks. They were then divided into four groups receiving distilled water, PIE (100 or 300 mg/kg/d), and pioglitazone (10 mg/kg/d) for a further six weeks, during which the HFFD was continued.

13‑‑retinoic acid inhibits the self‑renewal, migration, invasion and adhesion of cholangiocarcinoma cells.

13‑‑retinoic acid (13CRA), a Food and Drug Administration‑approved drug for severe acne, is currently being investigated for its potential use in skin cancer prevention. 13CRA has been reported to exhibit antitumor effects against various types of cancer cells, both and . However, to the best of our knowledge, no information is yet available regarding the effects of 13CRA on cholangiocarcinoma (CCA), a malignancy of the bile duct epithelia.

Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein.

Owing to the crucial role of Src in cancer metastasis, interruption of Src and its signaling has been considered a promising strategy for cancer metastasis treatment. Cucurbitacin B, a dietary triterpenoid, has been shown to possess anti-proliferative and apoptosis-inducing activities in cholangiocarcinoma (CCA) cells via suppressing the activation of FAK which is a main downstream Src effector. We hypothesized that cucurbitacin B might act as a Src suppressant which conferring anti-metastasis effect against CCA cells.

Epidermal growth factor receptor as a potential target of momordin Ic to promote apoptosis of cholangiocarcinoma cells.

Objectives: Strategies that induce apoptosis of malignant cells are recognized as effective cancer treatments. This study evaluated the apoptosis-inducing ability of momordin Ic against cholangiocarcinoma (CCA) cells and the respective underlying mechanisms.

Methods: Quantification of apoptotic cells was performed using Annexin V/7-AAD double dye staining followed by flow cytometry.

All--retinoic acid induces RARB-dependent apoptosis via ROS induction and enhances cisplatin sensitivity by NRF2 downregulation in cholangiocarcinoma cells.

All--retinoic acid (ATRA) has been clinically used to treat acute promyelocytic leukemia and is being studied to treat other types of cancer; however, the therapeutic role and mechanism of ATRA against cholangiocarcinoma (CCA) remain unclear. The present study investigated the cytotoxic effect and underlying mechanisms of ATRA on CCA cell lines. Cell viability was evaluated by sulforhodamine B assay.

Inhibition of FGFR2 enhances chemosensitivity to gemcitabine in cholangiocarcinoma through the AKT/mTOR and EMT signaling pathways.

Aim: To investigate the oncogenic role of FGFR2 in carcinogenesis in cholangiocarcinoma (CCA) cells. In addition, the feasibility of using FGFR inhibitors in combination with standard chemotherapy was also explored for the chemosensitizing effect in CCA cells.

Main Methods: Five CCA cell lines were used to screen FGFR2 expression by Western immunoblotting.

Licochalcone A Induces Cholangiocarcinoma Cell Death Via Suppression of Nrf2 and NF-κB Signaling Pathways.

Objective: To investigate the anti-tumor effect of licochalcone A (LCA) on proliferation and migration in cholangiocarcinoma (CCA) cells and to elucidate their underlying mechanisms.

Methods: Human CCA cells, KKU-100, KKU-213, KKU-214, KKU-156, and KKU-452 were used to study effect of LCA on proliferation and migration by a cytotoxicity assay, wound healing assay. Reactive oxygen species levels were evaluated using DHE-fluorescent probes.

Derrischalcone suppresses cholangiocarcinoma cells through targeting ROS-mediated mitochondrial cell death, Akt/mTOR, and FAK pathways.

Chemotherapy is a palliative treatment for unresectable patients with cholangiocarcinoma (CCA). However, drug resistance is a major cause of the failure of this treatment. Derrischalcone (DC), a novel chalcone isolated from Derris indica fruit, has been shown pharmacologically active; though, the effect of DC on CCA is unknown.

Cucurbitacin B Diminishes Metastatic Behavior of Cholangiocarcinoma Cells by Suppressing Focal Adhesion Kinase.

Objective: Cholangiocarcinoma (CCA) is a malignant tumor with aggressive metastatic property resulted from dysregulation of metastasis-regulated signaling pathways. The aim of this study was to investigate the effect of cucurbitacin B on metastatic behavior of CCA cells through modulation of focal adhesion kinase (FAK) protein.

Methods: KKU-452 cells were treated with a specific FAK inhibitor, FAK inhibitor-14, or cucurbitacin B at various concentrations for 24 h.

Targeted Modulation of FAK/PI3K/PDK1/AKT and FAK/p53 Pathways by Cucurbitacin B for the Antiproliferation Effect Against Human Cholangiocarcinoma Cells.

Inadequate responses to traditional chemotherapeutic agents in cholangiocarcinoma (CCA) emphasize a requirement for new effective compounds for the treatment of this malignancy. This study aimed to investigate the antiproliferative property of cucurbitacin B on KKU-100 CCA cells. The determination of underlying molecular mechanisms was also carried out.

Phenformin inhibits proliferation, invasion, and angiogenesis of cholangiocarcinoma cells via AMPK-mTOR and HIF-1A pathways.

Phenformin (Phen), a potent activator of AMPK, is effective against some resistant cancers. This study evaluated the inhibition of proliferation, migration, invasion, and angiogenesis by Phen in aggressive cancer cells and investigated the underlying mechanism of the inhibition. Cholangiocarcinoma (CCA) KKU-156 and KKU-452 cells were used in this study.

Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate.

Pamidronate has been hypothesized to effectively inhibit cancer cell growth and metastasis in bone tissue. Furthermore, pamidronate (Pami) exerts various direct effects against several cancer cell types, including growth and migration. The present study aimed to determine the underlying mechanism of Pami's effect on the proliferation and migration of cholangiocarcinoma (CCA) cells.

Cellular adaptation mediated through Nrf2-induced glutamate cysteine ligase up-regulation against oxidative stress caused by iron overload in β-thalassemia/HbE patients.

Oxidative stress caused as a result of iron overload is implicated in clinical manifestation of beta-thalassemia/haemoglobin E (β-Thal/HbE). In this study, we investigated the cellular adaptation against oxidative stress in β-Thal/HbE patients. Twenty-four paediatric β-Thal/HbE patients and 22 healthy controls were recruited in the study.

Myricetin ameliorates cytokine-induced migration and invasion of cholangiocarcinoma cells via suppression of STAT3 pathway.

Aim Of Study: Cholangiocarcinoma (CCA) is an aggressive cancer with considerable metastatic potential. Various cytokines secreted by tumor cells or cells in the tumor environment can promote the metastasis of CCA. The aim of the present study was to investigate the effect of myricetin on the inhibition of cytokine-induced migration and invasion and the associated cellular mechanisms in human CCA cells.

The Inhibition Kinetics and Potential Anti-Migration Activity of NQO1 Inhibitory Coumarins on Cholangiocarcinoma Cells.

Altered expression of a cytosolic flavoenzyme NAD(P)H:quinone oxidoreductase-1 (NQO1) has been seen in many human tumors. Its remarkable overexpression in cholangiocarcinoma (CCA; an aggressive malignancy of the biliary duct system) was associated with poor prognosis and short survival of the patients. Inhibition of NQO1 has been proposed as a potential strategy to improve the efficacy of anticancer drugs in various cancers including CCA.

Mitochondrial division inhibitor-1 potentiates cisplatin-induced apoptosis via the mitochondrial death pathway in cholangiocarcinoma cells.

Aims: Mdivi-1, a selective Drp-1 inhibitor, impedes mitochondrial dynamics and suppresses cancer proliferation and progression. Cholangiocarcinoma (CCA) is a very aggressive malignancy which is refractory to chemotherapy. The study investigated the mechanism of the chemosensitizing effect of mdivi-1 in cholangiocarcinoma.

Metformin sensitizes cholangiocarcinoma cell to cisplatin-induced cytotoxicity through oxidative stress mediated mitochondrial pathway.

Aims: Metformin (Met), an essential antidiabetic agent, shows antitumor activity in some cancers. A previous study showed that Met enhanced cytotoxic activity of cisplatin (Cis) in cholangiocarcinoma (CCA) in association with the activation of AMP-activated protein kinase and suppression of Akt-mTOR. However, these effects do not entirely explain the observed chemosensitizing effect.

Cucurbitacin B induces mitochondrial-mediated apoptosis pathway in cholangiocarcinoma cells via suppressing focal adhesion kinase signaling.

Low efficacy and high resistance rate associated with existing chemotherapeutic drugs enforce a requirement for novel therapeutic strategies for extremely aggressive cholangiocarcinoma (CCA). In the present study, the apoptosis-inducing activity of cucurbitacin B, a compound derived from plants of Cucurbitaceae family, against KKU-100 CCA cells and the underlying mechanism mediating its effect were investigated. The results showed that cucurbitacin B significantly decreased CCA cells viability by induction of apoptosis.

Metformin enhances cisplatin induced inhibition of cholangiocarcinoma cells via AMPK-mTOR pathway.

Aims: AMP-activated protein kinase (AMPK) functions as a cellular energy sensor regulating various aspects of cellular metabolism. Metformin (Met), an activator of AMPK, has been reported to reduce the cancer risk and enhance antitumor effects in certain cancers. Cholangiocarcinoma (CCA) is an aggressive malignancy which rarely responds to chemotherapeutic agents.