Differential Response of Akt to Cyclic AMP Modulates Drug Sensitivity(Molecular and Cell Biology)
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概要
- 論文の詳細を見る
Although Akt is known to be associated with drug resistance, its role in cyclic AMP (cAMP)-related inhibition of cell proliferation is not clear. Here, we report that Akt modulates the sensitivity of hepatocellular carcinoma cells to cAMP. Treatment of hepatocellular carcinoma cell lines (HepG_2 and Bel-7402) with cAMP inhibited proliferation, with HepG_2 cells showing lower sensitivity to cAMP. Biochemical studies showed that cAMP increased FBS-stimulated Akt phosphorylation in HepG_2 cells, but completely inhibited FBS-stimulated Akt phosphorylation in Bel-7402 cells, suggesting that the differential response of Akt to cAMP in these two cell lines might contribute to their differential sensitivity. LY294002, a phosphatidylinositol 3-kinase inhibitor that inhibits FBS-stimulated Akt phosphorylation, restored the sensitivity of HepG_2 cells to cAMP and API-2 (Akt/protein kinase B signaling inhibitor-2) also showed similar effect. These results collectively indicate that the response level of Akt to cAMP may play a critical role in determining drug sensitivity.
- 公益社団法人日本薬学会の論文
- 2006-07-01
著者
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Lou Liguang
Shanghai Institute Of Materia Medica Chinese Academy Of Sciences
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Lou Liguang
Shanghai Institute Of Materia Medica Shanghai Institute For Biological Sciences Chinese Academy Of S
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ZHAO Yunyu
Shanghai Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences
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Zhao Yunyu
Shanghai Institute Of Materia Medica Shanghai Institute For Biological Sciences Chinese Academy Of Sciences
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- Differential Response of Akt to Cyclic AMP Modulates Drug Sensitivity(Molecular and Cell Biology)