TAILIEUCHUNG - Báo cáo sinh học: "Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations | Niehr et al. Journal of Translational Medicine 2011 9 76 http content 9 1 76 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Combination therapy with vemurafenib PLX4032 RG7204 and metformin in melanoma cell lines with distinct driver mutations 1 112 1 11 Franziska Niehr Erika von Euw Narsis Attar Deliang Guo Doug Matsunaga Hooman Sazegar Charles Ng I A rd I S r 1 3 11 I -X A D X r I z 4 Dz V c I z 3 5 D -s I I I c 12 3 D z-x r m I A V S r-J I 11X 3 6 -X A 4- - . I D I L Sr 1 3 6 John A Glaspy Juan A Recio Roger S Lo Paul S Mischel Begonya Comin-Anduix and Antoni Ribas Abstract Background A molecular linkage between the MAPK and the LKB1-AMPK energy sensor pathways suggests that combined MAPK oncogene inhibition and metabolic modulation of AMPK would be more effective than either manipulation alone in melanoma cell lines. Materials and methods The combination of the BRAF inhibitor vemurafenib formerly PLX4032 and metformin were tested against a panel of human melanoma cell lines with defined BRAF and NRAS mutations for effects on viability cell cycle and apoptosis. Signaling molecules in the MAPK PI3K-AKT and LKB1-AMPK pathways were studied by Western blot. Results Single agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status but in one NRASQ61K mutant cell line it powerfully stimulated cell growth. Synergistic anti-proliferative effects of the combination of metformin with vemurafenib were observed in 6 out of 11 BRAFV600E mutants including highly synergistic effects in two BRAFV600E mutant melanoma cell lines. Antagonistic effects were noted in some cell lines in particular in BRAFV600E mutant cell lines resistant to single agent vemurafenib. Seven out of 8 BRAF wild type cell lines showed marginally synergistic anti-proliferative effects with the combination and one cell line had highly antagonistic effects with the combination. The differential effects were not dependent

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