科研之友
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摘要
The ubiquitously expressed serine-threonine kinase Akt and the transcription factor NF-kappa B both are involved in cell proliferation and apoptosis. Furthermore, the activation of Akt or NF-kappa B has been suggested to associate with chemoresistance of human tumors. The exact mechanism and interreaction of Akt and NF-kappa B pathway on chemoresistance in gastric cancer is still unknown. We explored the function of Akt and NF-kappa B pathway on chemoresistance in human gastric cancer cells. MTT method was used to analyze the influence of chemotherapeutics and the combined use of wortmannin or MG-132 on the growth of SGC-7901 cells. Apoptosis of SGC-7901 was detected by TUNEL and Annexin V/PI methods. The protein level of NF-kappa B was analyzed by immunocytochemical staining. EMSA was used to confirm the increased nuclear translocation of RelA. The protein level of p-Akt and p-I kappa B alpha were analyzed by Western blotting. Etoposide and doxorubicin suppressed the growth of SGC-7901 time and dose-dependently. Combined use of wortmannin or MG-132 can suppress growth further. Chemotherapeutics induced apoptosis of SGC-7901 and activated Akt and NF-kappa B, combined use of wortmannin or MG-132 induced apoptosis further and attenuated the activation of NF-kappa B. The combined use of wortmannin attenuated the activation of Akt, but combined use of MG-132 did not attenuate the activation of Akt. The activation of NF-kappa B is a branch mechanism of Akt anti-apoptosis effects. The chemotherapeutics induced apoptosis and induced the activation of Akt and NF-kappa B in SGC-7901 cell, suppression the activation of Akt or NF-kappa B can increase the effects of chemotherapeutics. NF-kappa B is a downstream target of Akt.
