Radiotherapy is a major therapeutic strategy for lung cancer, and radiation resistance (radioresistance) is an important cause of residual and recurring cancer after treatment. However, the mechanism of radioresistance remains unclear. Mitochondrial autophagy (mitophagy), an important selective autophagy, plays an important role in maintaining cell homeostasis and affects the response to therapy. Recent studies have shown that dihydroartemisinin (DHA), a derivative of artemisinin, can increase the sensitivity to treatment in multiple types of cancer, including lung cancer. The purpose of this study was to elucidate the function and molecular mechanisms of DHA-regulating mitophagy and DHA-reducing radioresistance in lung cancer A549 cells. We first constructed the radioresistant lung cancer A549 cells model (A549R) through fractional radiation, then elucidated the function and mechanism of DHA-regulating mitophagy to reduce the radioresistance of lung cancer by genomic, proteomic, and bioinformatic methods. The results showed that fractional radiation can significantly induce radioresistance and mitophagy in A549 cells, DHA can reduce mitophagy and radioresistance, and the inhibition of mitophagy can reduce radioresistance. Protein chip assay and bioinformatics analysis showed the following: Cold-Inducible RNA Binding Protein (CIRBP) might be a potential target of DHA-regulating mitophagy; CIRBP is highly expressed in A549R cells; the knockdown of CIRBP increases the effect of DHA, reduces mitophagy and radioresistance, and inhibits the mitophagy-related PINK1/Parkin pathway. In conclusion, we believe that DHA reduces radiation-induced mitophagy and radioresistance of lung cancer A549 cells via CIRBP inhibition.
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http://dx.doi.org/10.3390/life12081129 | DOI Listing |
Clin Cancer Res
January 2025
Moffitt Cancer Center, Tampa, Florida, United States.
Purpose: Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared to tumors with lower RAS---RAF interaction.
View Article and Find Full Text PDFMol Biol Evol
January 2025
Shmunis School of Biomedicine and Cancer Research, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Bats have adapted to pathogens through diverse mechanisms, including increased resistance - rapid pathogen elimination, and tolerance - limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead to increased resistance to infection.
View Article and Find Full Text PDFClin Cancer Res
January 2025
Istituti Fisioterapici Ospitalieri, Italy.
Background: The role of activating alterations in the MAPK pathway in predicting immunotherapy efficacy in lung squamous cell carcinoma (LSCC) patients is largely unknown. The aims of the randomized, phase II SQUINT trial were to assess the efficacy of nivolumab plus ipilimumab (NI) versus platinum-based chemotherapy plus nivolumab (N-CT) and to identify clinically available biomarkers of response to immunotherapy in patients with advanced or metastatic LSCC.
Methods: SQUINT was an open-label, randomized, parallel, non-comparative, phase II trial of NI versus N-CT in chemo-naïve, metastatic or recurrent LSCC adult patients.
Discov Nano
January 2025
Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany.
Metastatic cancer cells undergo metabolic reprogramming, which involves changes in the metabolic fluxes, including endocytosis, nucleocytoplasmic transport, and mitochondrial metabolism, to satisfy their massive demands for energy, cell division, and proliferation compared to normal cells. We have previously demonstrated the ability of two different types of compounds to interfere with linchpins of metabolic reprogramming, Pitstop-2 and 1,6-hexanediol (1,6-HD). 1,6-HD disrupts glycolysis enzymes and mitochondrial function, enhancing reactive oxygen species production and reducing cellular ATP levels, while Pitstop-2 impedes clathrin-mediated endocytosis and small GTPases activity.
View Article and Find Full Text PDFInt J Colorectal Dis
January 2025
Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.
Purpose: Liver and lung metastases demonstrate distinct biological, particularly immunological, characteristics. We investigated whether preoperative complete blood count (CBC) parameters, which may reflect the immune system condition, predict early dissemination to the liver and lungs in colorectal cancer (CRC).
Methods: In this retrospective single-centre study, we included 268 resected CRC cases with complete 2-year follow-up and analysed preoperative CBC for association with early liver or lung metastasis development.
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