Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancer
Blockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is considered the frontline strategy for advanced NSCLC with EGFR mutations. However, acquired resistance to EGFR-TKI has been observed, resulting in disease progression and limited clinical benefit. Polyphyllin VII is the main...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-07-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861317300919 |
| _version_ | 1818520238439792640 |
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| author | Honggang Wang Zhenghua Fei Hao Jiang |
| author_facet | Honggang Wang Zhenghua Fei Hao Jiang |
| author_sort | Honggang Wang |
| collection | DOAJ |
| description | Blockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is considered the frontline strategy for advanced NSCLC with EGFR mutations. However, acquired resistance to EGFR-TKI has been observed, resulting in disease progression and limited clinical benefit. Polyphyllin VII is the main member of polyphyllin family, which has been demonstrated to show strong anticancer activity against carcinomas. The sensitizing effect and underlying mechanism of Polyphyllin VII against acquired EGFR-TKI resistant NSCLC are still unexplored. In the present study, we aim to examined the sensitizing effect of Polyphyllin VII to gefitinib by modulating P21 signaling pathway in gefitinib acquired resistant NSCLC in vitro and in vivo. Gefitinib sensitive PC-9 cells and gefitinib acquired resistant H1975 cells were used. Cell proliferation and Clonogenic assay, Cell cycle analysis, Western blotting analysis and xenograft treatment were carried out. Polyphyllin VII enhanced the anti-proliferative effects of gefitinib and gefitinib-induced G1 phase arrest by modulation of P21 signaling pathway in acquired gefitinib resistant cells in vitro and in vivo. Polyphyllin VII elevated sensitization of gefitinib acquired resistant NSCLC cells to gefitinib through G1 phase arrest and modulation of P21 signaling pathway. It provides a potential new strategy to overcome gefitinib acquired resistance for EGFR-TKI resistant NSCLC. |
| first_indexed | 2024-12-11T01:34:38Z |
| format | Article |
| id | doaj.art-e59836655e7b4048be0a16e74ff851cd |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-11T01:34:38Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-e59836655e7b4048be0a16e74ff851cd2022-12-22T01:25:15ZengElsevierJournal of Pharmacological Sciences1347-86132017-07-01134319019610.1016/j.jphs.2017.06.005Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancerHonggang Wang0Zhenghua Fei1Hao Jiang2Department of Respiration, Jinhua People's Hospital, Jinhua, Zhejiang 321000, PR ChinaDepartment of Radiotherapy and Chemotherapy, The 1st Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, Zhejiang 325000, PR ChinaDepartment of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, PR ChinaBlockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is considered the frontline strategy for advanced NSCLC with EGFR mutations. However, acquired resistance to EGFR-TKI has been observed, resulting in disease progression and limited clinical benefit. Polyphyllin VII is the main member of polyphyllin family, which has been demonstrated to show strong anticancer activity against carcinomas. The sensitizing effect and underlying mechanism of Polyphyllin VII against acquired EGFR-TKI resistant NSCLC are still unexplored. In the present study, we aim to examined the sensitizing effect of Polyphyllin VII to gefitinib by modulating P21 signaling pathway in gefitinib acquired resistant NSCLC in vitro and in vivo. Gefitinib sensitive PC-9 cells and gefitinib acquired resistant H1975 cells were used. Cell proliferation and Clonogenic assay, Cell cycle analysis, Western blotting analysis and xenograft treatment were carried out. Polyphyllin VII enhanced the anti-proliferative effects of gefitinib and gefitinib-induced G1 phase arrest by modulation of P21 signaling pathway in acquired gefitinib resistant cells in vitro and in vivo. Polyphyllin VII elevated sensitization of gefitinib acquired resistant NSCLC cells to gefitinib through G1 phase arrest and modulation of P21 signaling pathway. It provides a potential new strategy to overcome gefitinib acquired resistance for EGFR-TKI resistant NSCLC.http://www.sciencedirect.com/science/article/pii/S1347861317300919P21Acquired resistanceNSCLCPolyphyllinCell cycle |
| spellingShingle | Honggang Wang Zhenghua Fei Hao Jiang Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancer Journal of Pharmacological Sciences P21 Acquired resistance NSCLC Polyphyllin Cell cycle |
| title | Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancer |
| title_full | Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancer |
| title_fullStr | Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancer |
| title_full_unstemmed | Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancer |
| title_short | Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancer |
| title_sort | polyphyllin vii increases sensitivity to gefitinib by modulating the elevation of p21 in acquired gefitinib resistant non small cell lung cancer |
| topic | P21 Acquired resistance NSCLC Polyphyllin Cell cycle |
| url | http://www.sciencedirect.com/science/article/pii/S1347861317300919 |
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