Potent Anti-tumor Effect And Mechanisms Of A Novel Antagonist Peptide Targeting HPV16E7

Human papilloma virus type16(HPV16) E7is a viral oncoprotein that is believedto play a major role in cervical neoplasia, the second largest cause of cancer death inwomen worldwide. As this viral protein is not expressed in normal cells, E7hasbecome an important research target for the therapy of HPV-related neoplasms. Noveltreatment strategies are urgently required due to the efficacy limitation and adverseeffects of current therapeutic strategies. In this study, with the aim of obtainingreagents that could be utilized in HPV-associated tumor therapy, we focused onscreening the c7c phage display peptide library for antagonist peptides against HPV16E7, and studying the anti-tumor efficacy and mechanisms so as to set foundation ofclinical medicine development.In our study, an antagonist peptide against HPV16E7protein, named Pep-7, wasfirst identified. In addition, anti-tumor function and mechanisms of the selected peptidewere also revealed both in vitro and in vivo. Firstly, the function of Pep-7in vitro wasstudied. The binding specificity and affinity of the selected peptide to HPV16E7weretested by competitive ELISA. The peptide showes significant cell proliferationinhibition with high specificity on HPV16-positive cells in the MTT and clonogenicassay. Secondly, to elucidate the mechanisms of the antagonist peptide, a series ofcytological tests, molecular experiments and biochemical assay were performed. Thestudy ascribed the anti-tumor effect of Pep-7to two main pathways.â‘ Pep-7inducesHPV16E7protein degradation and disrupts its association with pRb, which stabilizespRb, restores the pRb/E2F pathway, and induces cell cycle arrest consequently.â‘¡Pep-7leads to marked apoptosis through p53augmentation linked with p21expressionpromotion, as a consequence of its interaction with HPV16E7. Finally, Pep-7showsevident therapeutic efficacy through the same mechanisms on tumor xenografts as oncells.In light of these results, there is strong evidence that the selected peptide is a"good candidate" for the treatment of HPV16-related neoplasms...