Chelerythrine Inhibits TGF-β-Induced Epithelial–Mesenchymal Transition in A549 Cells via RRM2
<b>Background:</b> The mechanisms underlying the metastasis of non-small-cell lung cancer (NSCLC) have long been a focal point of medical research. The anti-tumor effects of chelerythrine (CHE) have been confirmed; however, its ability to inhibit tumor metastasis and the underlying mecha...
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2025-07-01
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| author | Jinlong Liu Mengran Xu Liu Han Yuxuan Rao Haoming Han Haoran Zheng Jinying Wu Xin Sun |
| author_facet | Jinlong Liu Mengran Xu Liu Han Yuxuan Rao Haoming Han Haoran Zheng Jinying Wu Xin Sun |
| author_sort | Jinlong Liu |
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| description | <b>Background:</b> The mechanisms underlying the metastasis of non-small-cell lung cancer (NSCLC) have long been a focal point of medical research. The anti-tumor effects of chelerythrine (CHE) have been confirmed; however, its ability to inhibit tumor metastasis and the underlying mechanisms remain unknown. The aim of this study was to investigate the inhibitory effects and molecular mechanisms of CHE on transforming growth factor-beta (TGF-β)-induced epithelial–mesenchymal transition (EMT). <b>Methods</b>: Wound healing and Transwell assays were employed to evaluate TGF-β-induced migration in A549 cells and the inhibitory effects of CHE. Ribonucleotide reductase subunit M2 (RRM2) expression levels were detected via Western blot and immunofluorescence staining. Western blot and RT-qPCR were used to examine the expression levels of EMT-related markers. Animal experiments were conducted to analyze the role of RRM2 in the CHE inhibition of TGF-β-induced lung cancer metastasis. <b>Results</b>: This study found that TGF-β treatment enhanced the metastasis of A549 cells, while CHE inhibited the expression of TGF-β-induced EMT-related transcription factors by RRM2, thereby suppressing tumor cell migration (<i>p</i> < 0.05). Furthermore, the oral administration of CHE inhibited the metastasis of A549 cells to the lungs from the tail vein in mice, consistent with in vitro findings. Despite the high doses of CHE used, there was no evidence of toxicity. <b>Conclusions</b>: Our data reveal the mechanism of the anti-metastatic effects of CHE on TGF-β-induced EMT and indicate that CHE can be used as an effective anti-tumor treatment. |
| format | Article |
| id | doaj-art-1736303cba8c48649fc856cb5fefceaf |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-1736303cba8c48649fc856cb5fefceaf2025-08-20T03:56:46ZengMDPI AGPharmaceuticals1424-82472025-07-01187103610.3390/ph18071036Chelerythrine Inhibits TGF-β-Induced Epithelial–Mesenchymal Transition in A549 Cells via RRM2Jinlong Liu0Mengran Xu1Liu Han2Yuxuan Rao3Haoming Han4Haoran Zheng5Jinying Wu6Xin Sun7School of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, ChinaSchool of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, ChinaSchool of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, ChinaSchool of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, ChinaSchool of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, ChinaSchool of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, ChinaSchool of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, ChinaSchool of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, China<b>Background:</b> The mechanisms underlying the metastasis of non-small-cell lung cancer (NSCLC) have long been a focal point of medical research. The anti-tumor effects of chelerythrine (CHE) have been confirmed; however, its ability to inhibit tumor metastasis and the underlying mechanisms remain unknown. The aim of this study was to investigate the inhibitory effects and molecular mechanisms of CHE on transforming growth factor-beta (TGF-β)-induced epithelial–mesenchymal transition (EMT). <b>Methods</b>: Wound healing and Transwell assays were employed to evaluate TGF-β-induced migration in A549 cells and the inhibitory effects of CHE. Ribonucleotide reductase subunit M2 (RRM2) expression levels were detected via Western blot and immunofluorescence staining. Western blot and RT-qPCR were used to examine the expression levels of EMT-related markers. Animal experiments were conducted to analyze the role of RRM2 in the CHE inhibition of TGF-β-induced lung cancer metastasis. <b>Results</b>: This study found that TGF-β treatment enhanced the metastasis of A549 cells, while CHE inhibited the expression of TGF-β-induced EMT-related transcription factors by RRM2, thereby suppressing tumor cell migration (<i>p</i> < 0.05). Furthermore, the oral administration of CHE inhibited the metastasis of A549 cells to the lungs from the tail vein in mice, consistent with in vitro findings. Despite the high doses of CHE used, there was no evidence of toxicity. <b>Conclusions</b>: Our data reveal the mechanism of the anti-metastatic effects of CHE on TGF-β-induced EMT and indicate that CHE can be used as an effective anti-tumor treatment.https://www.mdpi.com/1424-8247/18/7/1036chelerythrinenon-small-cell lung cancerepithelial–mesenchymal transitionRRM2 |
| spellingShingle | Jinlong Liu Mengran Xu Liu Han Yuxuan Rao Haoming Han Haoran Zheng Jinying Wu Xin Sun Chelerythrine Inhibits TGF-β-Induced Epithelial–Mesenchymal Transition in A549 Cells via RRM2 Pharmaceuticals chelerythrine non-small-cell lung cancer epithelial–mesenchymal transition RRM2 |
| title | Chelerythrine Inhibits TGF-β-Induced Epithelial–Mesenchymal Transition in A549 Cells via RRM2 |
| title_full | Chelerythrine Inhibits TGF-β-Induced Epithelial–Mesenchymal Transition in A549 Cells via RRM2 |
| title_fullStr | Chelerythrine Inhibits TGF-β-Induced Epithelial–Mesenchymal Transition in A549 Cells via RRM2 |
| title_full_unstemmed | Chelerythrine Inhibits TGF-β-Induced Epithelial–Mesenchymal Transition in A549 Cells via RRM2 |
| title_short | Chelerythrine Inhibits TGF-β-Induced Epithelial–Mesenchymal Transition in A549 Cells via RRM2 |
| title_sort | chelerythrine inhibits tgf β induced epithelial mesenchymal transition in a549 cells via rrm2 |
| topic | chelerythrine non-small-cell lung cancer epithelial–mesenchymal transition RRM2 |
| url | https://www.mdpi.com/1424-8247/18/7/1036 |
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