Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells
Endostar is a human recombinant endostatin which is an attractive anti-angiogenesis protein. Because inefficient antigen presenting MHC class I expression (which can be downregulated by HIF-1) is an important strategy for cancer immune evasion, besides its anti-angiogenesis effect, it remains unclea...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Cancer Biology & Therapy |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2025.2508535 |
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| author | Ming-Zhen Zhao Hong-Fei Zheng Jing-Na Wang Yan-Min Zhang Hai-Jing Wang Zhi-Wei Zhao |
| author_facet | Ming-Zhen Zhao Hong-Fei Zheng Jing-Na Wang Yan-Min Zhang Hai-Jing Wang Zhi-Wei Zhao |
| author_sort | Ming-Zhen Zhao |
| collection | DOAJ |
| description | Endostar is a human recombinant endostatin which is an attractive anti-angiogenesis protein. Because inefficient antigen presenting MHC class I expression (which can be downregulated by HIF-1) is an important strategy for cancer immune evasion, besides its anti-angiogenesis effect, it remains unclear whether Endostar has an inhibitory effect on HIF-1 expression by upregulating MHC class I expression in cancer cells to facilitate immunotherapies, including PD-1/PD-L1 inhibitors. In this study, A549 and NCI-H1299 lung cancer cells were treated with Endostar (6.25 μg/ml, 12.5 μg/ml, and 25 μg/ml, respectively). HIF-1 expression was detected by Immunocytochemistry and Western blot. Proteins of the MHC class I α-heavy chain and β2 m light chain, STAT3 and pSTAT3 were detected by Western blot. The mRNAs of MHC class I α-heavy chain and β2 m light chain were detected by RT-qPCR. It was shown that decreased expression of HIF-1 and promotion of β2-microglobulin were observed after Endostar treatment. In addition, elevated levels of MHC class I α-heavy chain mRNA and protein, as well as downregulation of STAT3 and pSTAT3, were also observed following Endostar treatment. Endostar inhibited HIF-1 expression in A549 and NCI-H1299 lung cancer cells, upregulated expression of MHC class I α-heavy chain and β2 m light chain, with the upregulation of STAT3 and pSTAT3, suggesting involvement of STAT3 pathway. It is important because only in combination with MHC class I on target cells can tumor antigenic peptides be recognized by CD8+ CTLs which destroy target cells. However, MHC class I is frequently deficient in cancer cells. |
| format | Article |
| id | doaj-art-6db28441f53d47799dbce8f187e79d90 |
| institution | Kabale University |
| issn | 1538-4047 1555-8576 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj-art-6db28441f53d47799dbce8f187e79d902025-08-20T03:47:41ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762025-12-0126110.1080/15384047.2025.2508535Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cellsMing-Zhen Zhao0Hong-Fei Zheng1Jing-Na Wang2Yan-Min Zhang3Hai-Jing Wang4Zhi-Wei Zhao5Hebei Key Laboratory of Panvascular Diseases, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaEndostar is a human recombinant endostatin which is an attractive anti-angiogenesis protein. Because inefficient antigen presenting MHC class I expression (which can be downregulated by HIF-1) is an important strategy for cancer immune evasion, besides its anti-angiogenesis effect, it remains unclear whether Endostar has an inhibitory effect on HIF-1 expression by upregulating MHC class I expression in cancer cells to facilitate immunotherapies, including PD-1/PD-L1 inhibitors. In this study, A549 and NCI-H1299 lung cancer cells were treated with Endostar (6.25 μg/ml, 12.5 μg/ml, and 25 μg/ml, respectively). HIF-1 expression was detected by Immunocytochemistry and Western blot. Proteins of the MHC class I α-heavy chain and β2 m light chain, STAT3 and pSTAT3 were detected by Western blot. The mRNAs of MHC class I α-heavy chain and β2 m light chain were detected by RT-qPCR. It was shown that decreased expression of HIF-1 and promotion of β2-microglobulin were observed after Endostar treatment. In addition, elevated levels of MHC class I α-heavy chain mRNA and protein, as well as downregulation of STAT3 and pSTAT3, were also observed following Endostar treatment. Endostar inhibited HIF-1 expression in A549 and NCI-H1299 lung cancer cells, upregulated expression of MHC class I α-heavy chain and β2 m light chain, with the upregulation of STAT3 and pSTAT3, suggesting involvement of STAT3 pathway. It is important because only in combination with MHC class I on target cells can tumor antigenic peptides be recognized by CD8+ CTLs which destroy target cells. However, MHC class I is frequently deficient in cancer cells.https://www.tandfonline.com/doi/10.1080/15384047.2025.2508535EndostarHIF-1MHC-Iβ2mlung cancer |
| spellingShingle | Ming-Zhen Zhao Hong-Fei Zheng Jing-Na Wang Yan-Min Zhang Hai-Jing Wang Zhi-Wei Zhao Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells Cancer Biology & Therapy Endostar HIF-1 MHC-I β2m lung cancer |
| title | Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells |
| title_full | Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells |
| title_fullStr | Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells |
| title_full_unstemmed | Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells |
| title_short | Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells |
| title_sort | inhibitory effect of endostar on hif 1 with upregulation of mhc i in lung cancer cells |
| topic | Endostar HIF-1 MHC-I β2m lung cancer |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2025.2508535 |
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