Role of p38 <scp>MAPK</scp> in enhanced human cancer cells killing by the combination of aspirin and <scp>ABT</scp>‐737

Zhang, Chong; Shi, Jing; Mao, Shi-Ying; Yan, Xu; Zhang, Dan; Feng, Linqing; Zhang, Bo; Yan, Youyou; Wang, Sicong; Pan, Jianping; Yang, Yanmei; Lin, Nengming

doi:10.1111/jcmm.12461

Cited by 31 publications

(23 citation statements)

References 27 publications

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“…Furthermore, the ERK signaling pathway in addition to the p38 signaling pathway may regulate numerous factors that are associated with cancer progression and poor prognosis in NSCLC (31)(32)(33). The MMP family comprises 24 zincdependent endopeptidases, and serves important roles in tumor metastasis and MMP26 is associated with the invasion and metastasis of non-small cell lung cancer (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 18 promotes proliferation and migration of H460 cells via the ERK and p38 signaling pathways

et al. 2016

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Abstract.Recently, fibroblast growth factor 18 (FGF18) expression was reported to be upregulated in colon cancer and ovarian cancer, and increased expression of FGF18 mRNA and protein is associated with tumor progression and poor overall survival in patients; however, its role in lung cancer remains to be explored. In the present study, the effect and underlying molecular mechanisms of FGF18 on H460 cells were investigated. Cell proliferation and cell cycle alterations were detected using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometry. A wound healing assay was conducted to detect cell migration. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to measure extracellular signal-regulated kinase (ERK), p38 and matrix metalloproteinase 26 (MMP26) expression. Knockdown of FGF18 using short interfering RNA (siRNA-FGF18) suppressed H460 cell proliferation, inhibited cell migration via the downregulation of MMP26 levels, with siRNA-FGF18 additionally inhibiting the ERK and p38 signaling pathway. The present study indicates that FGF18 serves an essential role in the growth and migration of non-small cell lung cancer (NSCLC) cells by regulating the ERK, p38 signaling pathways and MMP26 protein levels, suggesting that FGF18 may be a potential molecular drug target for the treatment NSCLC.

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Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 18 promotes proliferation and migration of H460 cells via the ERK and p38 signaling pathways

et al. 2016

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“… found that long‐term combination treatment with aspirin and a small‐molecule Bcl‐2/Bcl‐xL antagonist (ABT‐737) could synergistically induce apoptosis both in A549 and H1299 cell lines. Meanwhile, combination treatment with short‐term aspirin and the small‐molecule Bcl‐2/Bcl‐xL antagonist (ABT‐737) caused a greater autophagic response than that to either drug alone, and autophagy switched from a cytoprotective signal to a death‐promoting signal . P38 acts as the cellular switch between these two different cell death pathways (i.e., autophagy and apoptosis) induced by cotreatment with aspirin and ABT‐737 .…”

Section: Autophagy: Novel Applications Of Nsaidsmentioning

confidence: 99%

“…In 2016, the US Preventive Services Task Force recommended low‐dose aspirin for preventing colorectal cancer (CRC) in patients without a bleeding tendency . More recently, several novel studies have examined NSAIDs and cancer , and some researchers found that NSAIDs are closely related to autophagy, especially in hepatocellular carcinoma (HCC) , glioblastoma , neuroblastoma , acute leukemia , lung adenocarcinoma , oral cancer , breast cancer , ovarian cancer, colon cancer , bladder cancer, and gastric cancer . In this article, we will review the mechanisms underlying the actions of NSAIDs in autophagy (Fig.…”

Section: Introductionmentioning

confidence: 99%

Autophagy: novel applications of nonsteroidal anti‐inflammatory drugs for primary cancer

Chen

Liu

et al. 2017

Cancer Medicine

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In eukaryotic cells, autophagy is a process associated with programmed cell death. During this process, cytoplasmic proteins and organelles are engulfed by double‐membrane autophagosomes, which then fuse with lysosomes to form autolysosomes. These autolysosomes then degrade their contents to recycle the cellular components. Autophagy has been implicated in a wide variety of physiological and pathological processes that are closely related to tumorigenesis. In recent years, an increasing number of studies have indicated that nonsteroidal anti‐inflammatory drugs, such as celecoxib, meloxicam, sulindac, aspirin, sildenafil, rofecoxib, and sodium salicylate, have diverse effects in cancer that are mediated by the autophagy pathway. These nonsteroidal anti‐inflammatory drugs can modulate tumor autophagy through the PI3K/Akt/mTOR, MAPK/ERK1/2, P53/DRAM, AMPK/mTOR, Bip/GRP78, CHOP/ GADD153, and HGF/MET signaling pathways and inhibit lysosome function, leading to p53‐dependent G1 cell‐cycle arrest. In this review, we summarize the research progress in autophagy induced by nonsteroidal anti‐inflammatory drugs and the molecular mechanisms of autophagy in cancer cells to provide a reference for the potential benefits of nonsteroidal anti‐inflammatory drugs in cancer chemotherapy.

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“…p38 MAPK (p38), one of three distinct families of MAPKs (ERK, JNK and p38 kinase), is a vital factor mediating ASA functions, such as ASA-induced anti-inflammatory and anticancer effects [10,11] . In addition, p38 activation is involved in the fibrosis of various organs.…”

Section: Introductionmentioning

confidence: 99%

Aspirin alleviates cardiac fibrosis in mice by inhibiting autophagy

Liu

Sun

et al. 2017

Acta Pharmacol Sin

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Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg -1 ·d -1, ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice. The mechanisms underlying ASA's anti-fibrotic effect were further analyzed in neonatal cardiac fibroblasts (CFs) exposed to hypoxia in vitro. ASA (0.5-5 mmol/L) dose-dependently inhibited the proliferation and Akt phosphorylation in the CFs. In addition, ASA significantly inhibited CF apoptosis, and decreased the levels of apoptosis markers (cleaved caspase 3 and Parp1), which might serve as a side effect of anti-fibrotic effect of ASA. Furthermore, ASA dose-dependently inhibited the autophagy in the CFs, as evidenced by the reduced levels of autophagy marker LC3-II. The autophagy inhibitor Pepstatin A (PepA) promoted the inhibitory effect of ASA on CF proliferation, whereas the autophagy inducer rapamycin rescued ASA-caused inhibition of CF proliferation, suggesting an autophagydependent anti-proliferative effect of ASA. Both p38 inhibitor SB203580 and ROS scavenger N-acetyl-cysteine (NAC) significantly decreased Akt phosphorylation in CFs in the basal and hypoxic situations, but they both significantly increased LC3-II levels in the CFs. Our results suggest that an autophagy-and p38/ROS-dependent pathway mediates the anti-cardiac fibrosis effect of ASA in CFs. As PepA and SB203580 did not affect ASA-caused inhibition of CF apoptosis, the drug combination will enhance ASA's therapeutic effects.

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Role of p38 MAPK in enhanced human cancer cells killing by the combination of aspirin and ABT‐737

Cited by 31 publications

References 27 publications

Fibroblast growth factor 18 promotes proliferation and migration of H460 cells via the ERK and p38 signaling pathways

Fibroblast growth factor 18 promotes proliferation and migration of H460 cells via the ERK and p38 signaling pathways

Autophagy: novel applications of nonsteroidal anti‐inflammatory drugs for primary cancer

Aspirin alleviates cardiac fibrosis in mice by inhibiting autophagy

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