Browsing by Subject "PI3K"

Now showing 1 - 3 of 3
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    High expression of the phosphoinositide 3-kinase p110γ isoform can predict poor prognosis of non-small cell lung cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Jung, Ina; Lee, Hyoun Wook; Roh, Mee Sook; Lee, Jae Seok; Kim, Kisu; Kim, Kyungeun; Kim, Tae Gyu; Nam, Hyun-Yeol
    The protein p110γ is an isoform of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration and have been implicated in the oncogenesis of various cancers. In this study, p110γ expression in non-small cell lung cancer (NSCLC) and its association with clinicopathological factors and patient survival were evaluated. A total of 230 NSCLC tumors were immunohistochemically stained for p110γ. Of these, 174 (75.7%) and 56 (24.3%) were placed in the low and high expression groups, respectively. The positive rate of p110γ was significantly higher in adenocarcinoma than in squamous cell carcinoma (p<0.001). Advanced stage NSCLCs showed higher p110γ expression than those at an early stage (p=0.002). Irrespective of the histological tumor type, the patients with high p110γ expression had significantly worse overall survival than those with low p110γ expression (p=0.004). p110γ expression was an independent poor prognostic factor in the multivariate analysis. Our results suggest that p110γ may be involved in the development and progression of NSCLC, and that p110γ has promising potential as a prognostic factor or novel therapeutic target for NSCLC.
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    Lysimachia christinae Hance aqueous extract ameliorates renal injury in kidney stone rats and calcium oxalate crystal-induced oxidative stress in HK-2 cells via inhibiting the PI3K/Akt/mTOR pathway
    (2026) Shengni Lv; Wangen Wang; Liangrong Zhu; Luning Lin; Xintian Zheng; Biología Celular e Histología
    Objectives. Kidney stones are a frequent urinary system disorder. Lysimachia christinae Hance is an accepted herb in traditional Chinese medicine for treating kidney stones. However, the effects and mechanisms of Lysimachia christinae Hance aqueous extract (LCH) are yet to be elucidated. Methods. The function of the aqueous extract of LCH was assessed using kidney stone rat models induced by 1% ethylene glycol+2% NH4Cl. Additionally, an in vitro model of human renal tubular epithelial cells (HK-2) treated with calcium oxalate was used. Results. Resultantly, the treatment of aqueous extract of LCH at different concentrations or LCH+LY294002 (PI3K-specific inhibitor) showed significant improve ment in inorganic ions and renal pathological injury in nephrolithiasis rats. Besides, consistent with the in vivo assay, LCH-containing serum increased cell viability and inhibited oxidative stress and deposition of Ca2+ in HK 2 cells, while the influences of LCH-containing serum were attenuated. Mechanistically, the aqueous extract of LCH and LCH-containing serum also promoted Nrf2 and HO-1 levels and inhibited the phosphorylated expression levels of PI3K, AKT, and mTOR. Conclusion. This study shows that LCH ameliorates the kidney damage in kidney stone rats and HK-2 cells. The mechanism of LCH in treating kidney stones is related to the activation of the Nrf2/HO-1 axis and the inhibition of the PI3K/Akt/mTOR pathway.
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    Role of MAP Kinases and PI3K-Akt on the cytokine inflammatory profile of peritoneal macrophages from ascites of cirrhotic patients
    (Wiley, 2013-01-20) Such, José; Francés, Rubén; García-Penarrubia, Pilar; Hernández Caselles, Trinidad; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Tapia Abellán, Ana; Bioquímica y Biología Molecular B e Inmunología
    Aims: Several new approaches targeting inflammation associated with different diseases are in clinical development. Objective: To explore the role played by MAPK and PI3K-Akt pathways on the release of cytokines in monocyte-derived macrophages (M-DM) obtained from the ascites of cirrhotic patients to identify novel targets for pharmaceutical intervention to prevent hepatic damage. Methods: M-DM were isolated from the ascites of cirrhotic patients and stimulated in vitro with LPS and heat-killed Candida albicans in the presence or absence of the inhibitors for MEK1, p38 MAPK, JNK and PI3K. The MAPK phosphorylation levels were determined by Western Blot. Cell culture supernatants were assayed by ELISA for TNF-α, IL-6 and IL-10. Results: The release of the pro-inflammatory cytokines IL-6 and TNF-α at baseline was more effectively reduced by the MAPK inhibitors, while the basal IL-10 anti-inflammatory cytokine secretion was only and strongly (90.3%) affected by the PI3K inhibitor. The incubation of peritoneal M-DM in the presence of LPS and C. albicans increased the release of IL-6, TNF-α and IL-10. LPS-induced pro-inflammatory cytokines secretion was more sensitive to MAPK inhibitors, whereas that induced by C. albicans was more susceptible to inhibition of PI3K. Finally, inhibition of PI3K almost completely suppressed the secretion of IL-10 in stimulated M-DM. Conclusions: These results demonstrate that pro-inflammatory cytokines release in M-DM from this clinical setting strongly depends on the MAPK signalling pathways, differs depending on the microbial stimulus added and confirms the prominent role of the PI3K-Akt pathway in the modulation of IL-10-mediated anti-inflammatory function.