Potential Role of MAPK Inhibitor in the Benzo(a)pyrene-Induced Anti-Apoptosis Against Cisplatin Treatment and Tumor Tumor Invasion of Papillary Thyroid Carcinoma Cells.
Yang Seok Chae, Kwang-Sung Ahn, Hyunji Kim, Nam Hee Won. Korea University College of Medicine, Seoul, Korea
Background: Background: Constitutive activation of the MAPK pathway through genetic alterations, including RAS and B-type RAF (BRAF) mutations, is common in human cancers and is associated with cell malignant transformation and aggressiveness, implicating that targeted inhibition of the MAPK pathway may potentially be an effective therapy for human cancers.
Design: Design: To investigate the role of B(a)P in the progression of papillary thyroid carcinoma, 8 primary cultured PTC cells were obtained from PTC patients and then examined the effects of B(a)P on activation of MAPK signaling using Western blot. B(a)P induced tumor invasion was examined using in vitro tumor invasion chamber and MMPs mRNA of invaded cells was then examined using real-time PCR.
Results: Results: Blockage of MAPK cell signaling successfully not only inhibits cisplatin-induced apoptosis but also partially suppresses ability of PTC cell invasion. And induction of phospho-JNK and phospho-ERK-1/2 were noted when primary PTC cells were treated with 1 nM B(a)P. In in vitro tumor invasion assay, B(a)P-induced PTC cell invasion was reduced by either PD98059 or JNK II inhibitor. PD98059 effectively inhibited B(a)P-induced tumor invasion when compared to control. The transcription luciferase reporter system demonstrated that PD98059 effectively reduced AP-1 activity when compared to control. The levels of MMP-2 and MMP-9 mRNA expression were reduced slightly by treatment with MEK inhibitor.
Conclusions: Conclusion: We conclude a significant association of PTC cell invasion when PTC cells continuously was exposed to B(a)P. Our findings suggest that MEK inhibitor may function as a small molecule inhibitor of tumor invasion and may provide novel mechanistic insights into the potential therapy for human PTC.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 40, Tuesday Afternoon