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Distinctive regulation and function of PI 3K/Akt and MAPKs in doxorubicin‐induced apoptosis of human lung adenocarcinoma cells
Author(s) -
Zhao Yanqiu,
You Han,
Yang Yu,
Wei Lin,
Zhang Xin,
Yao Libo,
Fan Daiming,
Yu Qiang
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10751
Subject(s) - protein kinase b , apoptosis , doxorubicin , p38 mitogen activated protein kinases , programmed cell death , mapk/erk pathway , kinase , cancer research , signal transduction , microbiology and biotechnology , pi3k/akt/mtor pathway , pharmacology , chemistry , biology , medicine , biochemistry , chemotherapy
Regulation and function of PI 3K/Akt and mitogen‐activated protein kinases (MAPKs) in doxorubicin‐induced cell death were investigated in human lung adenocarcinoma cells. Doxorubicin induced dose‐dependent apoptosis of human lung adenocarcinoma NCI‐H522 cells. Prior to cell death, both Akt and the MAPK family members (MAPKs: ERK1/2, JNK, and p38) were activated in response to the drug treatment. The kinetics of the inductions for Akt and MAPKs are, however, distinct. The activation of Akt was rapid and transient, activated within 30 min of drug addition, then declined after 3 h, whereas the activations of three MAPKs occurred later, 4 h after addition of the drug and sustained until cell death occurred. Inhibition of PI 3K/Akt activation had no effect on MAPKs' activation, suggesting that the two pathways are independently activated in response to the drug treatment. Inhibition of PI 3K/Akt and p38 accelerated and enhanced doxorubicin‐induced cell death. On the contrary, inhibition of ERK1/2 or JNK had no apparent effect on the cell death. Taken together, these results suggest that PI 3K/Akt and MAPKs signaling pathways are all activated, but with distinct mechanisms, in response to doxorubicin treatment. Activation of PI 3K/Akt and p38 modulates apoptotic signal pathways and inhibits doxorubicin‐induced cell death. These responses of tumor cells to cancer drug treatment may contribute to their drug resistance. Understanding of the mechanism and function of the responses will be beneficial for the development of novel therapeutic approaches for improvement of drug efficacy and circumvention of drug resistance. © 2003 Wiley‐Liss, Inc.