The Expression Of Ribosomal Protein L18 In Multiple Myeloma Cells And Its Effects On Proliferation Of Myeloma Cells

Background:Multiple myeloma(MM)is a malignant tumor characterized by massive plasma cell proliferation.It accounts for 10%～15% of the incidence of hematologic tumors and15%～20% of the mortality.Although drugs such as immunomodulators and proteasome inhibitors have greatly improved the prognosis of MM,almost all patients with MM have difficulty in treatment or relapse.Ribosomal protein L18(RPL18)is a component of the large subunit of ribosome.It not only plays an important role in ribosomal assembly,but also participates in a variety of extracorribosomal functions,that is,it participates in virus infection and regulation of cell differentiation and apoptosis.Recent studies have found that RPL18 plays an important role in the proliferation of some tumors,but its role in MM has not been reported.Therefore,this study will study the expression of RPL18 in MM cells and its effect on its proliferation,so as to provide ideas and basis for targeted therapy of MM.Objective:To demonstrate the expression of RPL18 in MM and its effect on the proliferation of MM cells in vitro.To screen out a Chinese medicine monomer targeting RPL18 to inhibit the proliferation of MM cells in vitro.Methods:Western blot and flow cytometry were used to detect the expression and membrane localization of RPL18 in 6 myeloma cells: PSR,U266,H929,RPMI8226,OPM2 and DR.The PSR was a borteomide resistant cell line,and its parent cell was U266.DR was a borteomi-resistant cell line,and its parent cell was RPMI8226.Using RPL18 knockdown Short hairpin RNA(Short hairpin RNA;Sh RNA)and lentivirus-packaged myeloma cells were transfected to detect the down-regulation effect of RPL18 on MM proliferation.The computer virtual screening molecular simulation docking technology was used to predict the sequence structure of RPL18,and the monomer inhibitors that might be combined with RPL18 were screened.Then,the effects of Chinese medicine monomer on the viability and proliferation of 6 kinds of MM cells were determined by cell culture experiments using MTS method and Western blot method.Result:1.It was confirmed that RPL18 could regulate the growth of multiple myeloma cells.2.The knockdown of RPL18 expression could inhibit the proliferation of MM cells and reduce the formation of clonal colonies.3.Forty-two monomers were obtained by computer virtual screening,and the effects of five traditional Chinese medicine monomers on myeloma cell proliferation were screened and detected: Rhmannioside D,Poliumoside,Ligustroflavone,Camelliaside A and Fructosylnystose.The results showed that Fructosylnystose(10μg/ml)and Camelliaside A(50μg/ml)had strong inhibitory effect on cells proliferation at 48 h,suggesting that RPL18 was involved in the proliferation of myeloma cells and was A potential target of traditional Chinese medicine for tumor inhibition.Conclusion:1.It is further demonstrated that RPL18 may be involved in the inhibition of the extracorribosomal function of tumorigenesis.2.Downregulation of RPL18 expression can inhibit multiple myeloma cell proliferation.3.The traditional Chinese medicine monomer--Camelliaside A and Fructosylnystose could inhibit the proliferation of MM cells by RPL18.4.RPL18 can be used as a potential biomarker and therapeutic target for MM.