Anticancer Activities Of Platinum Complexes With Schiff Base Ligand Targeted PTP1B

PTPs can maintain normal cell signal transduction by regulating the phosphorylation level of cells,which leads to the normalization of proliferation and apoptosis in vivo.Studies have shown that overexpression of PTPs in cancer cells leads to abnormal levels of intracellular phosphorylation and affects cell signaling.The induction of various diseases(such as cancer),thus effectively inhibiting the overexpression of PTPs in cancer cells will help the prevention and treatment of cancer,for which PTPs have gradually become one of the targets of cancer drug research.It is well known that platinum complexes have good cancer therapeutic effects,but most of these platinum complexes used for clinical treatment use DNA as a therapeutic target.Therefore,PTPs have been designed and screened to have highly effective anti-cancer activity targets.The platinum inhibitors provide new ideas for the development of anticancer drugs.Previous research group has screened three platinum complexes that can specifically inhibit PTP1 B by inhibiting the activity of recombinant PTPs.In this paper,we further studied the antitumor activity of this complex at the cellular level and used PTP1 B as a target.The main research content is as follows:1.Western Blot experiment was used to study the change of PTPs substrate phosphorylation level after three platinum complexes were applied to three different cells(MCF7,HepG2 and A549),and the expression of PTP1 B in different cells was detected..The experimental results show that the three complexes can effectively inhibit the activity of PTPs in cells,and the inhibitory effect is proportional to the concentration gradient of the complex;and complex 1 can make PTP1 B specifically bind to the substrate of pc-Src(Y529)phosphate The phosphorylation level of pc-Src(Y418),a specific binding substrate for TCPTP,did not change significantly,indicating that complex 1 can effectively and specifically inhibit the activity of intracellular PTP1B;furthermore,PTP1 B in different cells.The expression level did not change with the concentration of the complex,indicating thatcomplex 1 affected the change of substrate phosphorylation by inhibiting the activity of PTP1 B in cells,but did not inhibit the expression of PTP1 B in cells.2.The effect of three complexes on cell proliferation activity of different cells after 24 h and 48 h was studied by MTT colorimetry.The experimental results show that all three complexes can significantly inhibit the proliferation of MCF7 and HepG2 cells,and the higher the concentration of the complex and the longer the duration of the inhibition,the stronger the inhibitory effect on the proliferation of A549 cells;and the different complexes The inhibitory effect on proliferation of the same cell was different.Complex 1 had a stronger inhibitory effect on MCF7 than other complexes;the same complex had different effects on cell proliferation,and complex 1 had the most inhibitory effect on MCF7 cells.Strong,this may be due to the high expression of PTP1 B in MCF cells.3.Flow cytometry using Annexin V/PI double staining was used to study the effect of three complexes on different cells induced apoptosis after24 h.The experimental results show that with the increase of the complex concentration,the ability of the complex to induce apoptosis is gradually enhanced;the ability of the complex to induce apoptosis is stronger than that of the ligand;in the three complexes,the complex 1 induces the cell The ability to apoptosis is the strongest.4.The uptake of the three complexes in MCF7 cells after 24 h was measured by ICP-MS.The experimental results show that all three complexes can enter the cell,and the intake in the cells is significantly higher than that of cisplatin,especially the highest intake of complex 1,which may be the reason why the complex can effectively inhibit the proliferation of MCF cells.one.