| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Outline of Final Research Achievements |
In KRAS-mutated lung adenocarcinoma cells, the MEK inhibitors inhibited in vitro cell growth in a dose-dependent manner, and the growth inhibitory effect was enhanced by combination with the p38 inhibitors or small interfering RNAs (siRNAs) targeting MAPK14 that encodes p38α MAPK. These results indicate that combined inhibition of MEK and p38 could effectively suppress tumor growth of KRAS-mutated lung adenocarcinoma.
Meanwhile, it was found that programmed death receptor-ligand 1 (PD-L1), a ligand for the PD-1 receptor, is overexpressed in KRAS-mutated lung adenocarcinoma cell lines. In these cell lines, the PD-L1 expression was reduced either by siRNA-mediated knockdown of mutant KRAS or by inhibitors of MEK and ERK. These results indicate that oncogenic KRAS upregulates PD-L1 expression through the MEK-ERK pathway activation in lung adenocarcinoma cells. These findings provide rationales for developing therapeutic strategies against KRAS-mutated lung adenocarcinoma.
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