The Research About The Effect And Mechanism Of Small Molecule Compounds In Uveal Melanoma

OBJECTIVE: Uveal Melanoma(UM)is the most common malignant tumor in adults.It has a high degree of malignancy and is easily transferred through blood circulation.In the event of metastasis,the patients often die within 1 year.So a new treatment is urgent needed to improve the patient’s survival rate In this study,we wanted to screen out the small molecule compounds with inhibitory activity on UM cells.Through a series of experiments,we discussed the potential application value and the corresponding mechanism in the treatment of UM,and provided new ideas for the development of anticancer drugs.Methods: The small molecule compounds with inhibitory activity against UM cells were screened by high-throughput screening method.The effect of this compound on the proliferation of UM cells was detected by CCK8 assay and colony formation assay.The cell migration was detected by wound healing assay.And RNA-seq technique and drug target affinity reaction stabilization technique was used to detect the pre-treat and posttreat changes of UM cell on transcription and protein level;Use of molecular biology techniques to study the sequencing of a LncRNA PAUPAR function.Results: Through the high-throughput screening and a series of experiments,three kinds of compounds were selected as the target drug: 1090,1233,mith.1090 can inhibit the proliferation of UM cells,arrest the cell cycle,but the apoptotic cells did not increase;1233 can also inhibit the proliferation and migration of UM cells,arrest cell cycle and apoptotic cells also increased;mith also good at inhibiting the proliferation of UM cells.The results of RNA-seq showed that the mechanism of 1090 may be related to the regulation mechanism of cilia,and the analysis of protein spectrum shows that,after 1090 treatment,the various proteins related to metabolism has changed.Conclusion: We found three kinds of small molecule compounds,and confirmed their tumor suppressive effect in UM cells,and the mechanism of 1090 was carried out in the level of transcriptome and protein.This study enriches the potential medicinal value of three drugs and provides new possibilities for the development of anticancer drugs.