| Cancer is difficult to be diagnosed and prevented,with a high mortality rate.It has a serious threat to the health of human.And so many reseacher had put attention to study on cancer.Chemotherapy is an effective treatment.As we all know,Chemotherapy is used to treat cancer patients with chemicals.But there are many types of cancer.We often use different drugs to treat cancer,because different drugs treat different cancers with different effect.In these drugs to treat cancer,cisplatin because of its broad anti-cancer spectrum and significant anti-cancer effect,is widely used in cancer treatment,especially for testicular cancer,ovarian cancer with excellent therapeutic effect.However,cisplatin showed side-effect,such as neurotoxicity,kidney toxicity,ototoxic etc.So it is limited to be used in the course of treatment.Therefore,it's important that to study anti-cancer mechanism,toxicity and drug-resistance and other mechanisms.Maybe,studying these mechanisms can reduce the toxicity,overcome drug resistance,make more effective use in treatment of cancer.At last,it will guide the development of new platinum drugs research.The main anticancer mechanism of cisplatin have three steps:accumulation in cells,hydrolysis activation,crosslinking with DNA.The accumulation of cisplatin in cells include cellular uptake and efflux.The hydrolysis activation is that the Cl of cisplatin is replaced with H2O.Cisplatin reacts with the target DNA through cisplatin and adjacent adenine or Guanine N7 atoms coordination.The stable platinum-DNA complex,resulting in DNA distortion,resulting in DNA damage,ultimately promote cancer cells apoptosis,to achieve the effect of treatment.In a recent study,three processes of anticancer activity of cisplatin were associated with some proteins,such as copper transporter CTR1,ATP7A/ATP7B,and cisplatin uptake and pumping.Cisplatin in the cell is hydrolyzed and activated easily with mercapto,nitrogen-containing molecules,such as glutathione,protein and other reactions.Cisplatin and protein response can lead to damage to protein function,which will lead to the protein-related signal pathway changes,affecting the function of cells,so the study of cancer cells which are mainly what protein and cisplatin reaction,for the study of cisplatin The anti-cancer mechanism,side effects,drug resistance and other issues have a very important significance.However,many types of intracellular protein,low content,not easy to enrich and separation,it is difficult to use conventional means to analyze.Therefore,a chemical probe based on cisplatin and connected to tetragonal iron oxide particles was designed to study proteins that in the cells were able to react with cisplatin.The chemical probe can binding to proteins in the intracellular.After that,we could magnetic enrichment the proteins in cell lysis solution.Lastly,we would analyze these proteins.The process is called proteomics analysis.First,we designed a probe of cisplatin analogs,replacing the two amino groups of cisplatin with propylenediamine and extending it out of an alkynyl group as a functional group for ligation.Then,we prepared a magnetic separation effect of the three iron oxide nanoparticles system,and its surface was modified to contain an azido.Azido and alkynyl groups can be used as click-chemistry-reaction to connect the two parts.Then,we can make cells were incubated with probe.And we obtain the protein-probe complex in cell lysis solution.Finally,we can detect the protein to obtain information about the proteome that is cross-linked with cisplatin-probe. |
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