Autophagy activity in cholangiocarcinoma is associated with anatomical localization of the tumor

Autor: Krisztina Schlachter, András Kiss, Gábor Lotz, Ildikó Illyés, Milán Csengeri, Gábor Lendvai, Katalin Borka, Zsuzsa Schaff, Tímea Szekerczés, Erzsébet Szabó
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Cancer Treatment
Biochemistry
Cholangiocarcinoma
Basal (phylogenetics)
Medicine and Health Sciences
Energy-Producing Organelles
Chemotherapeutic Agents
Aged
80 and over
Staining
Multidisciplinary
Tissue microarray
Cell Death
Liver Diseases
Cell Staining
Drugs
Hep G2 Cells
Middle Aged
Prognosis
Mitochondria
Gene Expression Regulation
Neoplastic
Oncology
Cell Processes
Hepatocellular carcinoma
Immunohistochemistry
Medicine
Beclin-1
Female
Oncology Agents
Cellular Structures and Organelles
Research Article
medicine.drug
Adult
Sorafenib
Autophagic Cell Death
Science
Antineoplastic Agents
Gastroenterology and Hepatology
Bioenergetics
Adenocarcinoma
Research and Analysis Methods
Cell Line
Tumor
Gastrointestinal Tumors
Autophagy
medicine
Humans
Proliferation Marker
Immunohistochemistry Techniques
Aged
Pharmacology
business.industry
Carcinoma
Biology and Life Sciences
Cancers and Neoplasms
Cell Biology
Hepatocellular Carcinoma
medicine.disease
Survival Analysis
Histochemistry and Cytochemistry Techniques
Bile Ducts
Intrahepatic
Ki-67 Antigen
Bile Duct Neoplasms
Tissue Array Analysis
Specimen Preparation and Treatment
Cell culture
Immunologic Techniques
Cancer research
Neoplasm Grading
business
Klatskin Tumor
Zdroj: PLoS ONE, Vol 16, Iss 6, p e0253065 (2021)
PLoS ONE
ISSN: 1932-6203
Popis: The presence of autophagy has been indicated in cholangiocarcinoma (CC), which disease has poor prognosis and limited treatment options. Recently, CC has been classified by anatomical localization as intrahepatic (iCC), perihilar (pCC) and distal (dCC), showing different clinical and molecular characteristics. Thus, our aim was to compare autophagy activity in CC samples resected from different anatomical locations. Further, we investigated whether autophagy could be modulated in cell lines originated from iCC and extrahepatic CC (eCC) following the treatments with autophagy inhibitory and inducing agents. Tissue microarrays were prepared from 70 CC (28 iCC, 19 pCC and 23 dCC), 31 adjacent non-tumorous and 9 hepatocellular carcinoma (HCC) samples. Autophagy markers LC3, p62 and Beclin1 as well as proliferation marker Ki-67 were monitored by immunohistochemistry and were associated with patients’ survival. Modulation of autophagy was investigated in cell lines originated from iCC (HuH-28), eCC (TFK-1) and HCC (HepG2) by treating the cells with chloroquine (CQ) for inhibition and with Rapamycin, 5-Fluorouracil (5-FU) and Sorafenib for induction of autophagy. Our results indicated an inhibited autophagy in iCC and pCC tumor tissues, whereas active autophagy seemed to occur in dCC, especially in samples displaying low Ki-67 index. Additionally, low level of Beclin1 and high level of Ki-67 were associated with poor overall survival in dCC, suggesting the prognostic role of these proteins in dCC. Beside a baseline autophagy detected in each cell line, Rapamycin and 5-FU induced autophagy in iCC and HepG2 cell lines, Sorafenib in iCC cells. A chemotherapy agent in combination with CQ decreased IC50 effectively in the cell lines where basal and/or induced autophagy were present. In conclusion, we revealed differences in the autophagy activities of CC tissues and cell lines originated from different anatomical locations, which might influence patients’ treatment. Our results also suggest a prognostic role of Beclin1 and Ki-67 in dCC.
Databáze: OpenAIRE
Externí odkaz: