The Study Of LRP16Involving In The Resistance Mechanisms Of Cervical Cancer Radiotherapy

Text: LRP16gene was cloned in1999by the People’s Liberation Army GeneralHospital, a human gene. In a previous study, we found that the inhibition of LRP16expression can increase the sensitivity of tumor cells to radiation and theradiation-induced apoptosis, but the exact mechanism is not clear. Recent studies foundthat high expression of NF-κB in many cell types are thought to the key factor to causeradioresistance of tumor cells. Therefore, the inhibition of NF-κB signaling pathwaycan be used as a new helper method by enhancing the efficacy of radiotherapy withradiation treatment for cancer patients. However, it is not entirely clear that the specificmolecular mechanisms of NF-κB activity induced by ionizing radiation. In this study,LRP16may be a key molecule involving in the NF-κB activity induced by ionizingradiation. This study is divided into two parts.First LRP16Affects the Nuclear Translocation of NF-κB Induced byIonizing Radiation[Abstract] Objective: Our previous study showed that LRP16affected the nucleartranslocation of NF-κB induced by ionizing radiation in HeLa cells.Methods:immunofluorescence technique was used for determining the nuclear translocation ofNF-kappa B induced by IR at different time points. LRP16was overexpressed orknockdown in HeLa cells, and Western blot was performed on cell extracts to check theexpression of NF-kappa B, the degradation and phosphorylation of IκB-α. Results:NF-kappaB translocated into nucleus significantly at1hour point post-IR.Overexpression of LRP16promoted the nuclear translocation of NF-kappa B, thedegradation and phosphorylation of IκB-α. Otherwise, knockdown of LRP16inhibitedthe nuclear translocation of NF-kappa B, the degradation and phosphorylation of IκB-α. Conclusion: LRP16can affect the nuclear translocation of NF-kappa B induced by IRin HeLa cells. The study will provide a possible mechanism that how LRP16is involvedin radioresistance of cancer cells.Second LRP16Affects IR-Induced NF-κB Activity[Abstract] Objective: To study the role of LRP16in the signal transduction pathwaysof IR-induced nuclear factor-κB（NF-κB）activation. Methods: The role of LRP16onNF-κB response reporter(3×κB-Luc) and the target gene XIAP of NF-κB wasmeasured by Dual-luciferase Report Assay System and Western blot, respectively.Results: The Dual-luciferase Report Assay System showed that LRP16overexpressionpromoted the IR-induced relative luciferace activities of NF-κB response reporter (3×κB-Luc) and the inhibition of LRP16expression decreased the IR-induced relativeluciferace activities of NF-κB response reporter(3×κB-Luc); Western blot alsodemonstrated that LRP16overexpression promoted the expression of the anti-apoptoticgene XIAP induced by NF-κB and the inhibition of LRP16expression attenuated theexpression of the anti-apoptotic gene XIAP induced by NF-κB. Conclusion：LRP16canenhance NF-κB transcriptional activity induced by IR and affect the expression ofNF-κB-targeting anti-apoptotic gene XIAP induced by IR, which may provide an foundfor studying the molecular mechanism of IR-induced NF-κB transcriptional activation.