Comparison Of The Therapeutic Effects Of Lobaplatin And Carboplatin On Retinoblastoma In Vitro And In Vivo

PurposeRetinoblastoma(RB)is one of the most common primary intraocular malignancies in infants and young children,and chemotherapy is a conventional treatment for retinoblastoma.This study aims to explore the effects of lobaplatin and carboplatin on proliferation,apoptosis and tumor growth of retinal blasts.MethodsIn vitro experiments,MTT method was used to detect the effect of lobaplatin and carboplatin on the proliferation of retinal blasts;flow cytometry PI staining was used to detect the effect of lobaplatin and carboplatin on the cell cycle distribution of RB;Annexin v-FITC / Propidium iodide(PI)was performed to determine apoptosis;RNA-seq detection was used after using lobaplatin and carboplatin to analyze the expression of key transcripts in RB cells;reverse transcription polymerase chain reaction(RT-PCR)technique was used to detect the effects of lobaplatin and carboplatin on the expression of E2F1 / Cdc25 a / Cdk2 gene in RB cells.The retinoblastoma model of nude mice was constructed using Y79 cells,randomly divided into 4 groups,and received different drug treatments: group 1 was a control group,group 2 mice were injected with PBS,and group 3 mice were injected with carboplatin,mice in group 4 were injected with lobaplatin,the tumor growth curve was observed at 1/2/3/4 weeks,and pathological examination was performed after 4 weeks.ResultsAt high concentrations,carboplatin(80ug/ml)and lobaplatin(40ug/ml)significantly inhibited the proliferation of RB cells in vitro;compared with carboplatin,lobaplatin showed higher apoptosis in the early stage.In the flow cytometry test,no significant difference was observed in the S phase(carboplatin VS Lopatin 14.62 ± 0.60% VS 14.99 ± 1.20%(P = 0.7948))between these two groups.Compared with the NC group after intervention with carboplatin or Lopatin in RB cells,RNA-seq detected significant changes in the E2F1-Cdc25a-Cdk2 pathway.In the nude mouse model’s eye and subcutaneous tumors,the tumor growth was significantly inhibited.For example,after one week of administration,the tumor size of the control group was 48.42,the tumor cells broke through the basement membrane,and the epidermal expansion and growth occurred.The size of platinum tumors was 5.90 and 5.77,respectively,and tumor growth was significantly inhibited after carboplatin or Lopatin injection.Through PCR,immunofluorescence and immunohistochemical analysis in vitro and in vivo,it was found that the tendency of drugs to inhibit tumor pathological changes may be regulated by the E2F1-Cdc25aCdk2 pathway,while lobaplatin is more effective in controlling tumors in vivo.ConclusionThe lobaplatin has lower cytotoxicity in vitro and in vivo,and has better therapeutic effect than carboplatin.