PKM2 gene regulates the behavior of pancreatic cancer cells via mitogen-activated protein kinase pathways.
نویسندگان
چکیده
The aim of the current study was to investigate the effect of the PKM2 gene on the proliferation, invasion, migration and apoptosis of Panc‑1 and Sw1990 pancreatic cancer cells via its interaction with the mitogen‑activated protein kinases (MAPKs) signaling pathways. The expression levels of PKM2 protein in pancreatic cancer cells and the corresponding normal tissues was determined with western blot analysis. Immunohistochemical analysis of PKM2 expression was carried out in paraffin‑embedded sections of pancreatic cancer tissue. Two human pancreatic cancer cell lines were cultured in vitro, and a small interfering RNA (siRNA) was designed for the PKM2 gene and transfected into the cells. Cell proliferation was measured via an MTT assay, cell migration and invasion was measured via Transwell® chambers, and the effect of PKM2 on apoptosis was detected from B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein expression levels. Protein expression levels of the MAPK pathway proteins extracellular signal‑regulated kinase 1/2 (ERK1/2), p38 and c‑Jun N‑terminal kinase (JNK) and their phosphorylated forms were measured via western blot analysis. The expression level of PKM2 was significantly upregulated in the pancreatic cancer tissue compared with that of the corresponding normal tissue. Downregulation of PKM2 expression reduced the proliferation, migration and invasion of pancreatic cancer cell lines, while increasing the levels of apoptosis. Additionally, the expression levels of the phosphorylated‑(p‑)ERK1/2 and p‑p38 of the MAPK pathway in the PKM2 siRNA groups were markedly downregulated compared with those of the controls; however, the expression levels of ERK1/2, p38, JNK, p‑p38 and p‑JNK had no significantly changes compared with those of the control groups. In summary, the PKM2 gene has an important role in the proliferation, invasion, migration and apoptosis of Panc‑1 and Sw1990 pancreatic cancer cells, which may be associated with the expression of ERK1/2 and p38 of the MAPK signaling cascade.
منابع مشابه
Genistein Induces Apoptosis and Inhibits Proliferation of HT29 Colon Cancer Cells
Soybean isoflavone genistein has multiple anticancer properties and its pro-apoptotic and anti-proliferative effects have been studied in different cancer cells. However, the mechanisms of action of genistein and its molecular targets on human colon cells have not been fully elucidated. Therefore, caspase-3 and p38 mitogen-activated protein kinase (p38 MAPK) as the main therapeutic targets...
متن کاملThe Implication of Androgens in the Presence of Protein Kinase C to Repair Alzheimer’s Disease-Induced Cognitive Dysfunction
Aging, as a major risk factor of memory deficiency, affects neural signaling pathways in hippocampus. In particular, age-dependent androgens deficiency causes cognitive impairments. Several enzymes like protein kinase C (PKC) are involved in memory deficiency. Indeed, PKC regulatory process mediates α-secretase activation to cleave APP in β-amyloid cascade and tau proteins phosphorylation mecha...
متن کاملAnti-inflammatory Effects of Oxymatrine Through Inhibition of Nuclear Factor–kappa B and Mitogen-activated Protein Kinase Activation in Lipopolysaccharide-induced BV2 Microglia Cells
Oxymatrine, a potent monosomic alkaloid extracted from Chinese herb Sophora japonica (Sophora flavescens Ait.). possesses anti-inflammatory activittyes. This study was designed to investigate the effects of oxymatrine on nuclear factor–kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)-dependent inflammatory responses in lipopolysaccharide (LPS)-activated microglia. In this paper, BV2...
متن کاملRadiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions.
Radiotherapy represents a major treatment option for patients with pancreatic cancer, but recent evidence suggests that radiation can promote invasion and metastasis of cancer cells. Interactions between cancer cells and surrounding stromal cells may play an important role in aggressive tumor progression. In the present study, we investigated the invasive phenotype of pancreatic cancer cells in...
متن کاملPancreatic Cancer Cells through Tumor-Stromal Interactions Radiation to Stromal Fibroblasts Increases Invasiveness of Updated Version
Radiotherapy represents a major treatment option for patients with pancreatic cancer, but recent evidence suggests that radiation can promote invasion and metastasis of cancer cells. Interactions between cancer cells and surrounding stromal cells may play an important role in aggressive tumor progression. In the present study, we investigated the invasive phenotype of pancreatic cancer cells in...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Molecular medicine reports
دوره 11 3 شماره
صفحات -
تاریخ انتشار 2015