Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon / Chronic treatment with irinotecan activates the PI3K/AKT/mTOR pathway in HT-29 colon cancer xenografts

AUTOR(ES)

Kellen Ketty de Souza

DATA DE PUBLICAÇÃO

2007

RESUMO

Resistance of tumors to chemotherapeutic agents is a common clinical problem in human cancer. Recently, the blocking of PI3-kinase signaling pathway was shown to enhance apoptosis induced by SN-38, an active form of irinotecan. To gain further insight into the molecular events of irinotecan-associated increase in PI3-kinase signaling pathway, aspirin and rapamycin were used to modulate this signaling pathway. We describe here that aspirin is able to further inhibit IRS-l serine phosphorylation induced by irinotecan through targeting JNK and IKK, thus agonist activation of IRS-l/PI3-kinase pathway blocked the growth-inhibitory effect of irinotecan in HT -29 colon cancer xenografts; our data also demonstrate a synergistic effect of mTOR inhibition and irinotecan on tumor growth. Activation of PI3-kinase/ Akt/mTOR pathway may thus contribute to refTactoriness to treatment with irinotecan

ASSUNTO(S)

colonic neoplasms camptothecin neoplasias do colon camptotecina aspirina aspirin

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