Effects of blocking PI_3K-Akt signal pathway in reversion of cisplatin resistance in colon adenocarcinoma cell line
AIM: To evaluate whether Ly294002, suppressing phosphatidylinositol 3 kinase PI_3 K/Akt survival signaling pathway, can affect the level of YB-1 activity in the nuclei of acquired cisplatin-resistant colon adenocarcinoma cell line and subsequently restore the sensitivity of acquired cisplatin-resistant colon adenocarcinoma cell line to cisplatin (DDP). METHODS:A LS-174T cell line resistant to cisplatin was successfully established by exposing cells to increasing cisplatin concentrations ranging from 0.1 to 0.8 mg/L on an intermittent dosage schedule. The cisplatin resistant colon adenocarcinoma cell line was treated with Ly294002. The alteration of phosphated Akt (p-Akt) protein level was examined by Western blotting and intranuclear YB-1 transcriptional activity was examined by electrophoretic mobility shift assays ( EMSA ). The inhibition rates were determined by MTT assay. Cell apoptosis was evaluated by flow cytometry. RESULTS: After the inhibition of PI_3K/Akt signaling, Western blotting analysis revealed a dramatic decrease of p-Akt expression and this was correlated with decreased nuclear YB-1 activity in cisplatin-resistant cell line. Meanwhile, the apoptosis rate and cell growth inhibition rate were also increased in comparison with control cultures(P<0. 0H. CONCLUSION. The inhibition of PI_3K/Akt signal pathway may sensitize cisplatin-resistant cell line to DDP in vitro. PI_3, K/Akt pathway on the activation of YB-1 may play an important role in this process.
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