FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2894988107> ?p ?o ?g. }

• W2894988107 abstract "Background and purpose: The anti-diabetic biguanide drugs metformin and phenformin exhibit antitumor activity in various models. However, their radiomodulatory effect under hypoxic conditions, particularly for phenformin, is largely unknown. This study therefore examines whether metformin and phenformin as mitochondrial complex I blockades could overcome hypoxic radioresistance through inhibition of oxygen consumption. Material and methods: A panel of colorectal cancer cells (HCT116, DLD-1, HT29, SW480, and CT26) was exposed to metformin or phenformin for 16 hours at indicated concentrations. Afterwards, cell viability was measured by MTT and colony formation assays. Apoptosis and reactive oxygen species were detected by flow cytometry. Phosphorylation of AMP-activated protein kinase (AMPK) was examined by western blot. Mitochondria complexes activity and oxygen consumption rate were measured by seahorse analyzer. The radiosensitivity of tumor cells was assessed by colony formation assay under aerobic and hypoxic conditions. The in vitro findings were further validated in colorectal CT26 tumor model. Results: Metformin and phenformin inhibited mitochondrial complex I activity and subsequently reduced oxygen consumption rate in a dose-dependent manner starting at 3mM and 30μM respectively. As a result, the hypoxic radioresistance of tumor cells was counteracted by metformin and phenformin with an enhancement ratio about 2 at 9mM and 100μM respectively. Regarding intrinsic radioresistance, both of them did not exhibit any effect although there was an increase of phosphorylation of AMPK and reactive oxygen species production. In tumor-bearing mice, metformin or phenformin alone did not show any anti-tumor effect. While in combination with radiation, both of them substantially delayed tumor growth and enhanced radioresponse respectively by 1.3 and 1.5 folds. Conclusions: Our results demonstrate that metformin and phenformin overcome hypoxic radioresistance through inhibition of mitochondrial respiration, and provide a rationale to explore metformin and phenformin as hypoxic radiosensitizers." @default.
• W2894988107 created "2018-10-12" @default.
• W2894988107 creator A5000028376 @default.
• W2894988107 creator A5000316108 @default.
• W2894988107 creator A5009369215 @default.
• W2894988107 creator A5023765183 @default.
• W2894988107 creator A5037203692 @default.
• W2894988107 creator A5040579751 @default.
• W2894988107 creator A5062763774 @default.
• W2894988107 creator A5074877036 @default.
• W2894988107 creator A5080670960 @default.
• W2894988107 creator A5090366405 @default.
• W2894988107 creator A5091684230 @default.
• W2894988107 date "2018-10-03" @default.
• W2894988107 modified "2023-09-27" @default.
• W2894988107 title "Antidiabetic Biguanides Radiosensitize Hypoxic Colorectal Cancer Cells Through a Decrease in Oxygen Consumption" @default.
• W2894988107 cites W1536215703 @default.
• W2894988107 cites W1592486733 @default.
• W2894988107 cites W1809839416 @default.
• W2894988107 cites W1931273074 @default.
• W2894988107 cites W1961498002 @default.
• W2894988107 cites W1969043065 @default.
• W2894988107 cites W1978528142 @default.
• W2894988107 cites W1982217309 @default.
• W2894988107 cites W1991842062 @default.
• W2894988107 cites W1995069275 @default.
• W2894988107 cites W1995265458 @default.
• W2894988107 cites W1996182515 @default.
• W2894988107 cites W2001403424 @default.
• W2894988107 cites W2009077807 @default.
• W2894988107 cites W2009542601 @default.
• W2894988107 cites W2013687768 @default.
• W2894988107 cites W2015088299 @default.
• W2894988107 cites W2016133306 @default.
• W2894988107 cites W2020474316 @default.
• W2894988107 cites W2028114269 @default.
• W2894988107 cites W2039212784 @default.
• W2894988107 cites W2047516613 @default.
• W2894988107 cites W2056270851 @default.
• W2894988107 cites W2073399837 @default.
• W2894988107 cites W2076908467 @default.
• W2894988107 cites W2080654617 @default.
• W2894988107 cites W2088122814 @default.
• W2894988107 cites W2091042007 @default.
• W2894988107 cites W2104942855 @default.
• W2894988107 cites W2113327941 @default.
• W2894988107 cites W2114797316 @default.
• W2894988107 cites W2115220652 @default.
• W2894988107 cites W2117157143 @default.
• W2894988107 cites W2119437574 @default.
• W2894988107 cites W2123838717 @default.
• W2894988107 cites W2130592216 @default.
• W2894988107 cites W2135617839 @default.
• W2894988107 cites W2143681046 @default.
• W2894988107 cites W2146471707 @default.
• W2894988107 cites W2148608739 @default.
• W2894988107 cites W2148755064 @default.
• W2894988107 cites W2148764180 @default.
• W2894988107 cites W2157607856 @default.
• W2894988107 cites W2158731007 @default.
• W2894988107 cites W2160571820 @default.
• W2894988107 cites W2167436791 @default.
• W2894988107 cites W2170273562 @default.
• W2894988107 cites W2179686101 @default.
• W2894988107 cites W2195370592 @default.
• W2894988107 cites W2235653829 @default.
• W2894988107 cites W2314784059 @default.
• W2894988107 cites W2323045903 @default.
• W2894988107 cites W2411692156 @default.
• W2894988107 cites W2412718576 @default.
• W2894988107 cites W2417470860 @default.
• W2894988107 cites W2431330324 @default.
• W2894988107 cites W2468775570 @default.
• W2894988107 cites W2499786133 @default.
• W2894988107 cites W2504361340 @default.
• W2894988107 cites W2529806681 @default.
• W2894988107 cites W2560185130 @default.
• W2894988107 cites W2562100433 @default.
• W2894988107 cites W2593385553 @default.
• W2894988107 cites W2606333923 @default.
• W2894988107 cites W2606711458 @default.
• W2894988107 cites W2608623782 @default.
• W2894988107 cites W2746317954 @default.
• W2894988107 cites W2801100401 @default.
• W2894988107 cites W2804416221 @default.
• W2894988107 cites W321665048 @default.
• W2894988107 cites W943095070 @default.
• W2894988107 doi "https://doi.org/10.3389/fphar.2018.01073" @default.
• W2894988107 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6178882" @default.
• W2894988107 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30337872" @default.
• W2894988107 hasPublicationYear "2018" @default.
• W2894988107 type Work @default.
• W2894988107 sameAs 2894988107 @default.
• W2894988107 citedByCount "24" @default.
• W2894988107 countsByYear W28949881072019 @default.
• W2894988107 countsByYear W28949881072020 @default.
• W2894988107 countsByYear W28949881072021 @default.
• W2894988107 countsByYear W28949881072022 @default.
• W2894988107 countsByYear W28949881072023 @default.
• W2894988107 crossrefType "journal-article" @default.

• next