Objective:To investigate the effects of paclitaxel combined with Ipatasertib on the proliferation,migration and epitheli-al-mesenchymal transition(EMT)of oral squamous cell carcinoma(OSCC)SCC-9 cells in vitro.Methods:SCC-9 cells were treated with paclitaxel and Ipatasertib repectively and in combination.CCK-8 test and EdU assay were used to detect cell proliferation ca-pacity.Cellular migration was detected by Transwell and scratch method.The protein expressions of E-cad,N-cad,Vimentin,AKT and NF-κB were detected by Western blot.Results:Paclitaxel of 0.5-32 μmol/L combined with Ipatasertib of 2.5 μmol/L(IC50)showed synergistic inhibitory effect on the proliferation of SCC-9 cells,the combination of paclitaxel and ipatasertib more significantly inhibited the migration,down-regulated the protein expression of AKT,NF-κB,N-cad and Vimentin,and up-regulated the protein expression of E-cad.Conclusion:The combination of paclitaxel and Ipatasertib may have synergistic inhibitory effects on the prolif-eration,migration and EMT of OSCC cells,the function may be ralated with the inhibition of PI3K/AKT signaling pathway.

Objective:To investigate the effects of paclitaxel combined with Ipatasertib on the proliferation,migration and epitheli-al-mesenchymal transition(EMT)of oral squamous cell carcinoma(OSCC)SCC-9 cells in vitro.Methods:SCC-9 cells were treated with paclitaxel and Ipatasertib repectively and in combination.CCK-8 test and EdU assay were used to detect cell proliferation ca-pacity.Cellular migration was detected by Transwell and scratch method.The protein expressions of E-cad,N-cad,Vimentin,AKT and NF-κB were detected by Western blot.Results:Paclitaxel of 0.5-32 μmol/L combined with Ipatasertib of 2.5 μmol/L(IC50)showed synergistic inhibitory effect on the proliferation of SCC-9 cells,the combination of paclitaxel and ipatasertib more significantly inhibited the migration,down-regulated the protein expression of AKT,NF-κB,N-cad and Vimentin,and up-regulated the protein expression of E-cad.Conclusion:The combination of paclitaxel and Ipatasertib may have synergistic inhibitory effects on the prolif-eration,migration and EMT of OSCC cells,the function may be ralated with the inhibition of PI3K/AKT signaling pathway.

This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation. Therefore, we chose the chicken myeloid gene, mitochondrial import protein 1 (mim-1), as a target to study the binding specificity between potential dual-Myb-binding sites. The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT, which contains two AACNG consensuses. Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand (complex F) ismore stable than that inthereverse strand (complex R). The principal component analysis (PCA) dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3 (R2R3), resulting in the dissociation of DNA from c-Myb in complex R at 330 K, triggered by the reduced electrostatic potential on the surface of R2R3. Furthermore, the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R, which affected on the hydrogen-bond formation ability between R2R3 and DNA, and directly resulted in the dissociation of DNA from R2R3. The steered molecular dynamics (SMD) simulation studies also suggested that the electrostatic potential, major groove width, and hydrogen bonds made major contribution to the DNA‍-specific recognition. In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand. This study indicates that the three-dimensional (3D) structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses, which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb, as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.
Molecular Dynamics Simulation ; Consensus ; DNA ; Hydrogen