Inhibition of phosphoinositide 3-kinase/Akt pathway decreases hypoxia inducible factor-1α expression and increases therapeutic efficacy of paclitaxel in human hypoxic gastric cancer cells
| Autor: | Jing Zhang, Yu‑Chen Yang, Wei-Xiong Chen, Jin‑Shui Zhu, Hua Guo, Ni Wei Chen |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty chemistry.chemical_compound paclitaxel medicine hypoxia inducible factor-1α Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide 3-kinase Oncogene biology Akt/PKB signaling pathway business.industry hypoxia Akt gastric cancer phosphoinositide 3-kinase Articles Oncology Paclitaxel chemistry Apoptosis Cancer cell Cancer research biology.protein business |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1074 |
| Popis: | The phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway plays an important role in cell proliferation, transformation, apoptosis, tumor growth and angiogenesis. Paclitaxel is commonly used to treat multiple human malignancies; however, the underlying mechanisms of paclitaxel in gastric cancer (GC) have not been fully investigated. In the present study, specimens from 45 GC and 36 chronic gastritis patients were collected, and the correlations of PI3K, phosphorylated-Akt (p-Akt) and hypoxia-inducible factor-1α (HIF-1α) expression with the clinicopathological characteristics of GC were analyzed by immunohistochemistry. The human SGC-7901 GC cells under hypoxic conditions were pretreated with the PI3K inhibitor, LY294002 (40 μM), and paclitaxel (0.1 μM). The expression levels of PI3K, p-Akt and HIF-1α were detected by quantitative polymerase chain reaction and western blotting. Cell proliferative activity and apoptosis were evaluated by the Cell Counting Kit-8 assay and flow cytometry. As a result, the rates of positive expression of PI3K, p-Akt and HIF-1α were significantly higher in GC compared with chronic gastritis patients (each P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|