The impact of Akt and nuclear factor kB pathway on chemoresistance of gastric cancer cell

Abstract

Objective To evaluate the role of Akt and nuclear factor （NF）-kB pathway in the development of chemoresistance in gastric cancer and the relation between Akt and NF-kB. Methods SGC-7901 cells were exposed to chemotherapeutic drugs （ doxorubicin and etoposide ） or chemotherapeutic drugs combined with Wortmannin or MCr132. The cell growth was detected using MTT method. The apoptosis of SGC-7901 cells was measured by TUNEL and Annexin V/PI methods. The protein level of NF-kB was analyzed by immunocytochemical staining. Electrophoretic mobility shift assay （EMSA） was used to confirm the increased nuclear translocation of NF-kB/P65. The protein levels of p-Akt and p-IkBa were determined by Western blotting. Results① Both chemotherapeutic drugs could obviously inhibit the growth of SGC-7901 cells in time-dose-dependent manner. Pretreatment of SGC-7901 cells with Wortmannin or MG-132 could promote this inhibitory effect. ② Both chemotherapeutic drugs could induce apoptosis of SGC-7901 and activate Akt and NF-kB in a close-dependent manner. Wortmannin or MG-132 pretreatment could enhance the apoptosis of SGC 7901 cells and bloke NF-kB activation induce by doxorubicin or etoposide.③ The activation of NF-kB was found in SGC-7901 cells stimulated with Wortmannin,but no activation of Akt was noted in those treated with MG-132. Conclusions The chemotherapeutic drugs can both induce apoptosis and activate Akt and NF-kB in SGC-7901 cells. The efficacy of chemotherapeutic drugs can be increased via inhibiting activation of Akt or NF-kB. Key words: Stomach neoplasms; Chemotherapy; Drug resistance