Hyperoside markedly inhibited diffuse epidermal hyperplasia and significantly reduced the changes in phosphorylated levels of PI3K, AKT, mTOR and AMPK while reducing p38 phosphorylation as well as of tumor burden <i>in vivo</i> in DMBA/TPA induced skin tumors.
Subsequently, TNF-α and p38MAPK expression in tissue samples from 83 patients with HCC classified as T<sub>1</sub>N<sub>0</sub>M<sub>0</sub>, using the Tumour-Node-Metastasis (TNM) staging system, was investigated using immunohistochemistry.
Finally, we found that LMP1-positive EVs could promote tumor growth and P38 inhibition eliminates this promoting effect in vivo, and EV formation is associated with a poor prognosis in NPC patients.
Tumor specific microenvironment including inflammatory factors is key mediator for maintaining the stemness of CSCs through various pathways such as p38 MAPK.
Based on our previous findings that mutant <i>KRAS</i> knockdown sensitized NSCLC cells to a p38 inhibitor, the growth-inhibitory effect of dual MEK and p38 inhibition on tumor growth in NSCLC cells harboring <i>KRAS</i> mutations was investigated.
Finally, ERK and p38 MAPK phosphorylations were fourfold and threefold greater than control muscle 4 weeks following tumour implantation, respectively.
Here, it is demonstrated that phenobarbital treatment results in dephosphorylation of a tumor suppressor p38 MAPK in the liver of C57BL/6 and C3H/HeNCrlBR mice.
We hypothesized that SCLs, CAFs and MFBs would share common molecular signatures involving FOXO1, ROS and p38 MAPK and that their expression patterns were different from those tumors without monoallelic 13q14 deletion such as solitary fibrous tumors (SFTs).
The exact mechanism of vascular disruption is unknown; however, proposed direct and indirect mechanisms of action for DMXAA comprises (i) inducing apoptosis in endothelial cells; (ii) hemorrhagic necrosis and ischemia in tumor; (iii) release of serotonin (5-HT); (vi) stimulation of innate immune system; (v) production of inflammatory cytokines, for example TNF, IL-6, GCSF, KC, IP-10, and MCP-1; (vi) activation of NFκB and p38 (MAPK); (vii) production of nitric oxide; and (viii) reducing tumor energetics and membrane turnover.
The findings support the proposed role for P38 as a tumour suppressor in breast cancer via upregulation of DNA repair proteins and provide novel hypothesis-generating information on the potential role of P38 in adjuvant therapy decision making.
We discovered a positive feedback loop, in which the activation of p38 and AKT downstream from the altered FGFR3 upregulates <i>MYC</i> mRNA levels and stabilizes MYC protein, respectively, leading to the accumulation of MYC, which directly upregulates <i>FGFR3</i> expression by binding to active enhancers upstream from <i>FGFR3</i> Disruption of this FGFR3/MYC loop in bladder cancer cell lines by treatment with FGFR3, p38, AKT, or BET bromodomain inhibitors (JQ1) preventing <i>MYC</i> transcription decreased cell viability <i>in vitro</i> and tumor growth <i>in vivo</i> A relevance of this loop to human bladder tumors was supported by the positive correlation between <i>FGFR3</i> and <i>MYC</i> levels in tumors bearing <i>FGFR3</i> mutations, and the decrease in FGFR3 and MYC levels following anti-FGFR treatment in a PDX model bearing an <i>FGFR3</i> mutation.
Furthermore, the tumor growth rate, size and weight were markedly decreased and the survival time prolonged, following injection of DCs harboring miR‑128 mimic or p38 inhibitor in C57BL/6 mice bearing B16 melanoma.
Importantly, the levels of phosphorylated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were significantly increased but the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) was markedly decreased, which further promoted tumor protein 53 (p53) expression and inhibited nuclear factor E2-related factor 2 (Nrf2) expression.
Accumulating evidence suggests a dual role of p38 signaling in various types of cancers, wherein the p38 pathway can both suppress and promote tumor growth, metastasis and chemoresistance.
Silencing S100A6 using siRNA or shRNA significantly suppressed NPC cell proliferation, colony formation and p38/mitogen-activated protein kinase (MAPK) activity in vitro and inhibited tumor growth in a xenograft mouse model of NPC.
Our data suggest that insulin-dependent activation of p38 MAPK-p21 pathway is a possible mechanism responsible for delaying tumor growth in inactive mice.
We further demonstrated that inactivation of p38 is a potential mechanism contributing to acquisition and maintenance of cancer stem cell properties in non-small cell lung cancer (NSCLC) cells. p38, in particular the p38γ and p38δ isoforms, suppresses the cancer stem cell properties and tumor initiating ability of NSCLC cells by promoting the ubiquitylation and degradation of stemness proteins such as SOX2, Oct4, Nanog, Klf4 and c-Myc, through MK2-mediated phosphorylation of Hsp27 that is an essential component of the proteasomal degradation machinery.
Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase‑3, caspase‑3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl‑2), p38 mitogen‑activated protein kinase (p38 MAPK) and phosphorylated (p)‑p38 MAPK.