Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.

The Expression of GLUT-1 Glucose Transporter in the Immunohistological Distinction of Hepatocellular Carcinoma from Intrahepatic Cholangiocarcinoma / 한국간담췌외과학회지

BACKGROUND/AIMS: Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. We studied the expression of the glucose transporters in hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(CC). also, examined the usefulness of Glut-1 glucose transporter in the discrimination of HCC from CC. METHODS AND RESULTS: 23 HCC, 15 CC and 8 normal liver tissues were investigated immunohistochemically with Glut-1 glucose transporter. Immunostaning was regarded as positive when more than 5% of cells were stained. Among 38 liver tumor cases, Glut-1 was stained in 15(40%). in 2(9%) of 23 HCC and in 13(87%) of 15 CC were positive.(P=0.001) In HCC, underlying cirrhosis, 18(78%) were negative.(P=0.04) Other prognostic factors: histologic type, lymph node metastasis, distant metastasis did not show any significant correlation. CONCLUSION: Differential diagnosis between HCC and CC could be made by Glut-1 glucose transporter expression