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Background: Recombined humanized endostatin (Rh‐endostatin) exhibits a potent anti‐cancer effect involving multiple molecular targets and signaling pathways. HMGB1 is a highly conserved DNA‐binding protein involved in cancer development. The therapeutic effect of Rh‐endostatin on HMGB1 has not been reported, thus we investigate the effect in non‐small cell lung cancer (NSCLC) cells. Methods: Quantitative real‐time PCR and Western blot were used to analyze the messenger RNA and protein expression of HMGB1 in A549 cancer cells, while enzyme‐linked immunosorbent assay was used to detect the release of HMGB1. Western blot was performed to evaluate HMGB1 expression in SK‐MES‐1 and H661 NSCLC cells. Results: Rh‐endostatin inhibited the proliferation of A549 cancer cells and distinctly downregulated the expression and release of HMGB1 in dose and time dependent manners. Rh‐endostatin‐induced HMGB1 downregulation was confirmed in different types of NSCLC cells. Conclusion: These results demonstrate the general phenomenon that Rh‐endostatin can induce HMGB1 suppression in a variety of NSCLC cells. Rh‐endostatin may suppress HMGB1 expression and release in A549 cancer cells, thus inhibiting cell proliferation. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality. Therapies targeting programmed cell death 1 ligand 1 (PD1L1) have promising effects on NSCLC. However, resistance to targeted therapy has become the main problem and the underling molecular mechanism remains unclear. In the present study, the expression of PD1L1 in NSCLC was determined and the association with clinicopathological characteristics was analyzed. A combination therapy was also constructed, including pembrolizumab (Pem) and iodine-125 ( 125 I), which represented an efficient strategy for the treatment of NSCLC. The expression of PD1L1 was upregulated in NSCLC tissues and positively correlated with the Ki-67 index, pathological subtypes and risk stages. A higher level of PD1L1 expression was associated with poorer survival in patients with NSCLC, which could be used as a prognostic indicator. When NSCLC cells were cultured in the presence of Pem and 125 I seeds, the combination treatment significantly abrogated the tumor proliferation and aggressiveness through the inhibition of matrix metalloproteinase-2 and -9 secretion. Flow cytometry analysis revealed pembrolizumab combined with 125 I contributed to a higher rate of apoptosis and cell cycle arrest, indicating that the combination treatment improved the resistance to immunotherapy. Furthermore, the associated molecular mechanism was the dysregulation of ADAM metallopeptidase domain 17. The findings from the present study revealed that PD1L1 could be used as a predictive biomarker, and the application of combination treatment of pembrolizumab and 125 I showed promising effects on NSCLC., (Copyright © 2020, Spandidos Publications.)