Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NFκB activation

作者: Pei Yen Yeh , Shuang-En Chuang , Kun-Huei Yeh , Ying Chyi Song , Chee-Kwee Ea

DOI: 10.1016/S0006-2952(02)00908-5

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摘要: In this study, we showed that suppression of the MEK-ERK transduction pathway by a selective inhibitor, 2'-amino-3'-methoxyflavone (PD98059), increased drug resistance SiHa cells to cisplatin, but not another common anticancer drug, doxorubicin. The downstream mechanism discrepant cellular response was investigated. Both cisplatin and doxorubicin activated nuclear ERK2 transcription factor kappa B (NF B) cells. However, MEK-ERK2 PD98059 resulted in further enhancement cisplatin-induced NF activation, while no regulation noted doxorubicin-treated activation or due degradation cytoplasmic I alpha, as demonstrated western blotting. Transfection dominant negative alpha markedly diminished PD98059-induced Our results suggest signaling plays role chemosensitivity cells, increases partly via an increase activation. responsible for effect on hence towards remains be

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