4W, A Novel Naphthalimide-polyamine Conjugate, Anti-tumor Effects And Mechanisms Research In Vitro

Objective:Because the great difference of growth requirement for natural polyamines betweencancer cells and normal cells, natural polyamine is an ideal tumor targeting vector.Naphthalene imide can easily embed DNA, tumor cells and normal cells are different contentof DNA, which can be a target. Therefore, naphthalimide-polyamine conjugate should be atargeting drug. PI₃K/Akt signal pathway is an important intracellular signal transductionpathway. It plays important roles in cell apoptosis and survival by affecting the activity ofdownstream effector molecules, and it is closely associated with the development andprogression of human tumors. This paper mainly studies how the4W,which is a novelNaphthalimide-polyamine conjugate, induces by transfection of the Akt1colon cancer cellscompered with colon cancer cells in the proliferation, differentiation, survival, apoptosis,invasion, in terms of transfer and of the corresponding molecular mechanisms.Methods:Human colon cancer HCT116cell was selected as the research subject, first through genetransfection technology Akt1was transfected into HCT116cells. Cell growth ability assay,clone formation assay, cell movement test were used to investigate the role of Akt1gene inthe HCT116cells. The antitumor activity of4W was detected by MTT assay;AO/EB/Hoechst33342, PI/Hoechst33342, RH123/Hoechst33342and Lyso-TrackerRed/Hoechst33342staining were used to study the cell apoptosis of4W; The transwellexperiment was used to research the cell migration and invasion by4W; Western blotting wasused to measure the level of various protein, such as Caspase families, Bcl-2families,Cytochrome C, MMPs families. Results:Through the transfected Akt1HCT116cells compared with normal HCT116coloncancer cells, cell growth and proliferative capacity were increased, exercise capacity wasdecreased. In HCT116cells with or without akt1,4W has a growth inhibitory effect to them,which apoptosis was in a dose and time-dependent manner, and the transfected cells werebetter tolerated than normal cells. Through the transwell migration and invasion assay,4Wcan inhibit colon cancer cell migration and invasion, and it apoptosis was in a dose andtime-dependent manner. By staining experiments, it is found4W be able to induce tumor cellapoptosis. By western blot,4W can cause the activation of the caspase family, cytochrome crelease, activation of the Bcl-2family, induction of apoptosis, the formation of proteinexpression decreased VEGF, HIF-1α vascular invasion and metastasis of the MMP familyproteins expression was also reduced.Conclusion:Naphthalimide-polyamine conjugate4W can significantly induce apoptosis of coloncancer cells and inhibit colon cancer cell migration and invasion. The Akt1gene can promotethe proliferation of colon cancer cells, inhibit migration and invasion.