Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation and Apoptosis of Lung Adenocarcinoma Cell H1975
Background and objective Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib show promising therapeutic effects in patients with advanced non-small cell lung cancer (NSCLC). However, despite an initial response to EGFR-TKIs treatment among respon...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | zho |
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Chinese Anti-Cancer Association; Chinese Antituberculosis Association
2012-03-01
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| Series: | Chinese Journal of Lung Cancer |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.3779/j.issn.1009-3419.2012.03.01 |
| _version_ | 1818429837609533440 |
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| author | Xinyu ZHANG Guiyang LIU Xiaoguang ZHU Weilan WANG |
| author_facet | Xinyu ZHANG Guiyang LIU Xiaoguang ZHU Weilan WANG |
| author_sort | Xinyu ZHANG |
| collection | DOAJ |
| description | Background and objective Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib show promising therapeutic effects in patients with advanced non-small cell lung cancer (NSCLC). However, despite an initial response to EGFR-TKIs treatment among responsive patients, most inevitably acquire resistance after a progression-free period of about 10 months. The percentage of T790M in TKI acquired-resistant patients in most studies is around 50%. The aim of this study is to assess the effects of the sequential administration of docetaxel and gefitinib on cell proliferation and apoptosis of lung adenocarcinoma cell H1975. Methods An MTT assay was used to measure cell proliferation. The potency of the sequential administration of docetaxel and gefitinib were determined by isobolograms and combination index (CI). Cell apoptosis and cycle distribution were determined by flow cytometry. The Hoechst 33258 method was used to observe the apoptotic morphology. Chemical colorimetric luminescence was used to measure the caspase activity. Results The isobolograms and CI showed that the sequential administration of docetaxel following gefitinib remarkably inhibits cell proliferation and cell apoptosis compared with other sequential administration models. The cycle distribution results indicate that sequential docetaxel administration following gefitinib blocked the cells in the G2/M phase but not in the G0/G1. The activation of the Caspase-8/Caspase-3 cascade is mainly involved in the apoptotic pathway of lung adenocarcinoma cell H1975 in all sequential administration models. Conclusion The docetaxel administration following gefitinib might be a new stratagy for lung cancer with T790M mutation after having EGFR-TKIs resistance. |
| first_indexed | 2024-12-14T15:23:52Z |
| format | Article |
| id | doaj.art-160bde661f56452d8c8559c70853c350 |
| institution | Directory Open Access Journal |
| issn | 1009-3419 1999-6187 |
| language | zho |
| last_indexed | 2024-12-14T15:23:52Z |
| publishDate | 2012-03-01 |
| publisher | Chinese Anti-Cancer Association; Chinese Antituberculosis Association |
| record_format | Article |
| series | Chinese Journal of Lung Cancer |
| spelling | doaj.art-160bde661f56452d8c8559c70853c3502022-12-21T22:56:04ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34191999-61872012-03-0115312713810.3779/j.issn.1009-3419.2012.03.01Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation
and Apoptosis of Lung Adenocarcinoma Cell H1975Xinyu ZHANGGuiyang LIUXiaoguang ZHUWeilan WANGBackground and objective Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib show promising therapeutic effects in patients with advanced non-small cell lung cancer (NSCLC). However, despite an initial response to EGFR-TKIs treatment among responsive patients, most inevitably acquire resistance after a progression-free period of about 10 months. The percentage of T790M in TKI acquired-resistant patients in most studies is around 50%. The aim of this study is to assess the effects of the sequential administration of docetaxel and gefitinib on cell proliferation and apoptosis of lung adenocarcinoma cell H1975. Methods An MTT assay was used to measure cell proliferation. The potency of the sequential administration of docetaxel and gefitinib were determined by isobolograms and combination index (CI). Cell apoptosis and cycle distribution were determined by flow cytometry. The Hoechst 33258 method was used to observe the apoptotic morphology. Chemical colorimetric luminescence was used to measure the caspase activity. Results The isobolograms and CI showed that the sequential administration of docetaxel following gefitinib remarkably inhibits cell proliferation and cell apoptosis compared with other sequential administration models. The cycle distribution results indicate that sequential docetaxel administration following gefitinib blocked the cells in the G2/M phase but not in the G0/G1. The activation of the Caspase-8/Caspase-3 cascade is mainly involved in the apoptotic pathway of lung adenocarcinoma cell H1975 in all sequential administration models. Conclusion The docetaxel administration following gefitinib might be a new stratagy for lung cancer with T790M mutation after having EGFR-TKIs resistance.http://dx.doi.org/10.3779/j.issn.1009-3419.2012.03.01T790MH1975IsobologramsDocetaxelGefitinibApoptosis |
| spellingShingle | Xinyu ZHANG Guiyang LIU Xiaoguang ZHU Weilan WANG Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation and Apoptosis of Lung Adenocarcinoma Cell H1975 Chinese Journal of Lung Cancer T790M H1975 Isobolograms Docetaxel Gefitinib Apoptosis |
| title | Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation
and Apoptosis of Lung Adenocarcinoma Cell H1975 |
| title_full | Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation
and Apoptosis of Lung Adenocarcinoma Cell H1975 |
| title_fullStr | Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation
and Apoptosis of Lung Adenocarcinoma Cell H1975 |
| title_full_unstemmed | Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation
and Apoptosis of Lung Adenocarcinoma Cell H1975 |
| title_short | Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation
and Apoptosis of Lung Adenocarcinoma Cell H1975 |
| title_sort | sequence dependent effect of docetaxel with gefitinib on the proliferation
and apoptosis of lung adenocarcinoma cell h1975 |
| topic | T790M H1975 Isobolograms Docetaxel Gefitinib Apoptosis |
| url | http://dx.doi.org/10.3779/j.issn.1009-3419.2012.03.01 |
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