04 March 2020 : Laboratory Research
Altered Mitochondrial Dynamics, Biogenesis, and Functions in the Paclitaxel-Resistant Lung Adenocarcinoma Cell Line A549/TaxolXiang Zhou1F, Rui Li1B, Ruohua Chen1C, Jianjun Liu1A*
Med Sci Monit 2020; 26:e918216
BACKGROUND: Chemoresistance is a primary hindrance for current cancer treatments. The influence of abnormal mitochondria in chemotherapy resistance is not well known. To explore the correlation between mitochondria and acquired chemoresistance, this work studied alterations in mitochondrial dynamics, biogenesis, and functions for paclitaxel-resistant cancer cell line A549/Taxol and its parental line A549.
MATERIAL AND METHODS: Mitochondrial morphology was observed by transmission electron microscopy and confocal microscopy. We measured the mitochondrial mass and mitochondrial membrane potential using fluorescent dyes. The glucose metabolic profile and ATP (adenosine triphosphate) content were determined by bioluminescent cell assays. Seahorse bio-energy analyzer XF24 was used to detect the mitochondrial respiratory function. The expressions of mitochondrial dynamics and biogenesis related genes were quantified using real-time polymerase chain reaction.
RESULTS: We observed fusion morphology of the mitochondrial network in A549/Taxol cells, with upregulation of fusion genes (Mfn1 and Mfn2) and downregulation of fission gene Fis1. In A549/Taxol cells, mitochondrial mass showed a significant decrease, while the mitochondrial biogenesis pathway was strongly activated. Despite the decreased mitochondrial membrane potential, the capability for mitochondrial respiration was not impaired in A549/Taxol cells.
CONCLUSIONS: Our study revealed a series changes of mitochondrial characteristics in paclitaxel-resistant cells. Mfn1 and Mfn2 and PGC-1α increased, while Fis1 expression and mitochondrial oxidative phosphorylation decreased in A549/Taxol cell lines. These changes to mitochondrial fusion, fission, and biological function contributed to the occurrence of paclitaxel resistance in tumor cells which induced paclitaxel resistance.
Keywords: Drug Resistance, Energy Metabolism, Mitochondria, paclitaxel, A549 cells, Drug Resistance, Neoplasm, GTP Phosphohydrolases, Membrane Potential, Mitochondrial, Microscopy, Confocal, Microscopy, Electron, Transmission, Mitochondrial Dynamics, Mitochondrial Membrane Transport Proteins, Mitochondrial Proteins, organelle biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha
01 February 2023 : EditorialEditorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread
Med Sci Monit 2023; 29:e939580
19 January 2023 : Clinical ResearchEvaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...
Med Sci Monit In Press; DOI: 10.12659/MSM.938892
19 January 2023 : Clinical ResearchDetermining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Q...
Med Sci Monit 2023; 29:e939238
27 December 2022 : Clinical ResearchEffect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...
Med Sci Monit 2022; 28:e938926
03 Feb 2023 : Clinical ResearchTreatment of Gingival Recession Defects with Pouch and Tunnel Technique Using Connective Tissue Graft and L...
Med Sci Monit In Press; DOI: 10.12659/MSM.938865
02 Feb 2023 : Clinical ResearchOnline Questionnaire-Based Study to Evaluate the Attitudes and Use of Rubber Dental Dams by Saudi Dental Pr...
Med Sci Monit In Press; DOI: 10.12659/MSM.938672
02 Feb 2023 : Database AnalysisPrognostic-Related Biomarkers in Pancreatic Ductal Adenocarcinoma Correlating with Immune Infiltrates Based...
Med Sci Monit In Press; DOI: 10.12659/MSM.938785
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292