Open AccessRole of p38 MAPK in enhanced human cancer cells killing by the combination of aspirin and ABT ‐737
Author(s) -
Zhang Chong,
Shi Jing,
Mao Shiying,
Xu Yasi,
Zhang Dan,
Feng Linyi,
Zhang Bo,
Yan Youyou,
Wang Sicong,
Pan Jianping,
Yang Youping,
Lin Nengming
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12461
Subject(s) - aspirin , autophagy , apoptosis , cancer , medicine , p38 mitogen activated protein kinases , colorectal cancer , combination therapy , cancer cell , pharmacology , cancer research , lung cancer , mapk/erk pathway , programmed cell death , signal transduction , chemistry , biology , oncology , microbiology and biotechnology , biochemistry
Abstract Regular use of aspirin after diagnosis is associated with longer survival among patients with mutated‐ PIK 3 CA colorectal cancer, but not among patients with wild‐type PIK 3 CA cancer. In this study, we showed that clinically achievable concentrations of aspirin and ABT ‐737 in combination could induce a synergistic growth arrest in several human PIK 3 CA wild‐type cancer cells. In addition, our results also demonstrated that long‐term combination treatment with aspirin and ABT ‐737 could synergistically induce apoptosis both in A549 and H1299 cells. In the meanwhile, short‐term aspirin plus ABT ‐737 combination treatment induced a greater autophagic response than did either drug alone and the combination‐induced autophagy switched from a cytoprotective signal to a death‐promoting signal. Furthermore, we showed that p38 acted as a switch between two different types of cell death (autophagy and apoptosis) induced by aspirin plus ABT ‐737. Moreover, the increased anti‐cancer efficacy of aspirin combined with ABT ‐737 was further validated in a human lung cancer A549 xenograft model. We hope that this synergy may contribute to failure of aspirin cancer therapy and ultimately lead to efficacious regimens for cancer therapy.