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[Sequence-dependent Effect of Triptolide with Gefitinib on the Proliferation
and Apoptosis of Lung Adenocarcinoma Cell H1975].
- Source :
-
Zhongguo fei ai za zhi = Chinese journal of lung cancer [Zhongguo Fei Ai Za Zhi] 2015 Oct 20; Vol. 18 (10), pp. 599-609. - Publication Year :
- 2015
-
Abstract
- Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) show promising therapeutic effects in patients with advanced non-small cell lung cancer (NSCLC). However, despite an initial response to 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 triptolide and geftinib on cell proliferation and apoptosis of lung adenocarcinoma cell H1975.<br />Methods: A MTT assay was used to measure cell proliferation. The potency of the sequential administration of triptolide and geftinib were determined by isobolograms and combination index (CI). Cell apoptosis and cycle distribution were detected by flow cytometry. The Hoechst 33258 method was used to observe the apoptotic morphology. Chemical colorimetric luminescence was used to measure the caspase activity.<br />Results: The results of isobolograms and CI showed that the sequential administration of triptolide following geftinib remarkably inhibited cell proliferation and cell apoptosis compared with other sequential administration models. The cycle distribution results indicated that sequential triptolide administration following geftinib blocked the cells in the G2/M phase but not in the G0/G1 phase. The activation of the Caspase-9/Caspase-3 cascade was mainly involved in the apoptotic pathway of lung adenocarcinoma cell H1975 in all sequential administration models.<br />Conclusions: The triptolide administration following geftinib might be a new therapeutic strategy for lung cancer with T790M mutation after having EGFR-TKIs resistance.
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- Subjects :
- Adenocarcinoma drug therapy
Adenocarcinoma genetics
Adenocarcinoma metabolism
Adenocarcinoma of Lung
Cell Line, Tumor
Epoxy Compounds pharmacology
ErbB Receptors genetics
ErbB Receptors metabolism
Gefitinib
Humans
Lung Neoplasms drug therapy
Lung Neoplasms enzymology
Lung Neoplasms genetics
Lung Neoplasms metabolism
Protein Kinase Inhibitors pharmacology
Adenocarcinoma physiopathology
Antineoplastic Agents pharmacology
Apoptosis drug effects
Cell Proliferation drug effects
Diterpenes pharmacology
Lung Neoplasms physiopathology
Phenanthrenes pharmacology
Quinazolines pharmacology
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1999-6187
- Volume :
- 18
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Zhongguo fei ai za zhi = Chinese journal of lung cancer
- Publication Type :
- Academic Journal
- Accession number :
- 26483331
- Full Text :
- https://doi.org/10.3779/j.issn.1009-3419.2015.10.01