Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer

Zhou, Ting; Zhang, Liying; He, Jianzheng; Miao, Zhiming; Li, Yangyang; Zhang, Yiming; Liu, Zhiwei; Zhang, Shang-Zu; Chen, Yan; Zhou, Gucheng; Liu, Yongqi

doi:10.3389/fimmu.2023.1133899

Cited by 9 publications

(5 citation statements)

References 214 publications

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“…As can be seen from the results presented in Figure 2 , radiation affected only HCT 116 and HT-29 cells to a significant extent with ~40% reduction in cell proliferation compared to the control, while MRC-5 and BxPC-3 cells did not respond significantly to treatments with radiation. Such a low rate of radiation-induced cell inactivation in these cell lines could be due to their inherent radiation resistance or to the effects of radiation in these cell lines tending to manifest at later time points [ 25 , 26 ].…”

Section: Resultsmentioning

confidence: 99%

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma

Bošković,

Dobričić,

Keta

et al. 2024

Pharmaceutics

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Apart from cytotoxicity, inhibitors of the COX-2 enzyme have demonstrated additional effects important for cancer treatment (such as radiosensitization of tumor cells and cell antimigratory effects); however, the relationship between the inhibition of other inflammation-related enzyme 5-LOX inhibitors and anticancer activity is still not well understood. In our study, the cytotoxicity of thirteen COX-2 and 5-LOX inhibitors previously presented by our group (1–13) was tested on three cancer cell lines (HCT 116, HT-29 and BxPC-3) and one healthy cell line (MRC-5). Compounds 3, 5, 6 and 7 showed moderate cytotoxicity, but good selectivity towards cancer cell lines. IC50 values were in the range of 22.99–51.66 µM (HCT 116 cell line), 8.63–41.20 µM (BxPC-3 cell line) and 24.78–81.60 µM (HT-29 cell line; compound 7 > 100 µM). In comparison to tested, commercially available COX-2 and 5-LOX inhibitors, both cytotoxicity and selectivity were increased. The addition of compounds 6 and 7 to irradiation treatment showed the most significant decrease in cell proliferation of the HT-29 cell line (p < 0.001). The antimigratory potential of the best dual COX-2 and 5-LOX inhibitors (compounds 1, 2, 3 and 5) was tested by a wound-healing assay using the SW620 cell line. Compounds 1 and 3 were singled out as compounds with the most potent effect (relative wound closure was 3.20% (24 h), 5,08% (48 h) for compound 1 and 3.86% (24 h), 7.68% (48 h) for compound 3). Considering all these results, compound 3 stood out as the compound with the most optimal biological activity, with the best dual COX-2 and 5-LOX inhibitory activity, good selectivity towards tested cancer cell lines, significant cell antimigratory potential and a lack of toxic effects at therapeutic doses.

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Section: Resultsmentioning

confidence: 99%

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma

Bošković,

Dobričić,

Keta

et al. 2024

Pharmaceutics

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“…The characteristics of the tumor stemness properties of NR5A2 are conducive to understanding the biological function of carcinogenesis in LUAD and have guiding significance for the study of drug resistance in advanced LUAD [ [38] , [39] , [40] ]. In addition to being beneficial for the diagnosis and treatment of LUAD, whether NR5A2 has the same biological characteristics as other types of adenocarcinoma is a question worthy of further study [ [41] , [42] , [43] , [44] , [45] ].…”

Section: Discussionmentioning

confidence: 99%

NR5A2 gene affects the overall survival of LUAD patients by regulating the activity of CSCs through SNP pathway by OCLR algorithm and immune score

Wu,

Chen,

Zeng

et al. 2024

Heliyon

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“…A novel teranostic approach against malignancy based on the identification and characterization of MtO and/or MtS/MtO-EVs carrying metabolic code should be established with the prognostic significance in conferring RR and metastatic potential dictated by NSCLC. The investigation of the functional connections between DNA repair and inflammation/immunity pathways that are physiologically affected during IR and contribute to post-irradiation cancer progression is highly important [ 123 ]. The clarification of the cross-talk between these cellular processes and their combined effects in RR and stemness will significantly extend our understanding of the mechanisms underlying the IR-related loss of stem cell function and will pave the way to innovative MtO and/or MtS/MtO-EV-based interventions to improve the lifespan and healthspan of the patients.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation: Challenges and Perspectives

Leonov,

Dorfman,

Pershikova

et al. 2024

Cancers

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During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC.

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Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer

Cited by 9 publications

References 214 publications

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma

NR5A2 gene affects the overall survival of LUAD patients by regulating the activity of CSCs through SNP pathway by OCLR algorithm and immune score

Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation: Challenges and Perspectives

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