Role of p38 MAPK in enhanced human cancer cells killing by the combination of aspirin and ABT-737
| Autor: | Lin-yi Feng, You-ping Yang, Chong Zhang, Jianping Pan, Dan Zhang, Jing Shi, Neng-ming Lin, Youyou Yan, Shi-ying Mao, Ya-si Xu, Bo Zhang, Si-cong Wang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Programmed cell death
Colorectal cancer p38 mitogen-activated protein kinases Apoptosis p38 Pharmacology p38 Mitogen-Activated Protein Kinases Piperazines Nitrophenols Cell Line Tumor Neoplasms medicine Autophagy Humans combination Aspirin Sulfonamides ABT-737 business.industry Biphenyl Compounds Cancer Cell Biology Original Articles medicine.disease Cancer cell Molecular Medicine business medicine.drug |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | Regular use of aspirin after diagnosis is associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA 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 PIK3CA 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text