Sequence-dependent Effect of Triptolide with Geiftinib on the Proliferation and Apoptosis of Lung Adenocarcinoma Cell H1975
10.3779/j.issn.1009-3419.2015.10.01
- VernacularTitle:雷公藤甲素与吉非替尼序贯应用对人肺腺癌细胞H1975存活及凋亡通路的影响
- Author:
ZHANG XINYU
1
;
LIU GUIYANG
;
LIU HAO
;
MA TAO
Author Information
1. 蚌埠医学院药学系
- Keywords:
T790M;
H1975;
Isobolograms;
Triptolide;
Getfinib;
Apoptosis
- From:
Chinese Journal of Lung Cancer
2015;(10):599-609
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective 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 atfer a progression-free period of about 10 months. hTe percentage of T790M in TKI acquired-resistant patients in most studies is around 50%. hTe aim of this study is to assess the effects of the sequential administration of triptolide and getfinib on cell proliferation and apoptosis of lung adenocarcinoma cell H1975. Methods A MTT assay was used to measure cell proliferation. hTe potency of the sequential ad-ministration of triptolide and getfinib were determined by isobolograms and combination index (CI). Cell apoptosis and cycle distribution were detected by lfow cytometry. hTe Hoechst 33258 method was used to observe the apoptotic morphology. Chemical colorimetric luminescence was used to measure the caspase activity. Results hTe results of isobolograms and CI showed that the sequential administration of triptolide following getfinib remarkably inhibited cell proliferation and cell apop-tosis compared with other sequential administration models. hTe cycle distribution results indicated that sequential triptolide administration following getfinib blocked the cells in the G2/M phase but not in the G0/G1 phase. hTe activation of the Cas-pase-9/Caspase-3 cascade was mainly involved in the apoptotic pathway of lung adenocarcinoma cell H1975 in all sequential administration models. Conclusion hTe triptolide administration following getfinib might be a new therapeutic strategy for lung cancer with T790M mutation atfer having EGFR-TKIs resistance.
