PAK4-PROTAC靶向降解药物PpD促进免疫细胞杀伤肾癌细胞的研究

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ABSTRACT：Objective To explore the potential aplication of PAK4-PROTAC targeted degradation drug（PpD） in renal cancer immunotherapy.MethodsTIMER 2.O and TISIDB databases were used to analyze the relationship among PAK4 expression，tumorpurityandabundanceof immunecelinfiltration inrenal tumor microenvironment（TEM）.Renalcancercell lines OS-RC-2，786-Oand ACHN were treated withO125and250nmol/LPpDandtheeffectsof Jurkatcellco-cultureonthe results were investigated.Thecellapoptosis was detected with flowcytometry，and theexpressionofprogrammedcelleath1 ligandl（PD-L1）inrenalcancercels wasdetected with immunoblotting.ResultsThe high expressionof PAK4 was positively relatedtoimmune purity，and inhibitedtheabundanceofimmune kilercels inTEM，such as CD8Tcells，CD4Tcells，atural killer cells and dendritic cells.With PpD treatment，there were 21.02% apoptotic cells in OS-RC-2，29. 67% （204 apoptotic cells in 786-O，and 15.39% apoptotic cells in ACHN，respectively.However，with the same concentration of 250 nmol/L PpD treatment，cell apoptotic rate was sharply increased to 70.13% in OS-RC-2/Jurkat， 70.68% in 780-O/Jurkat， and 60.27% in ACHN/Jurkat co-culture models，respectively.ConclusionPpD can promote apoptosis of renal cancer cells by reducing the expression of PAK4 protein，and enhance the killing effects of immune cells on tumor cells.

{EY WORDS ： renal cancer ; p21 activated kinases 4; PAK4-PROTAC targeted degradation drug；co-culture； immunotherapy

摘要：目的探讨 p21激活激酶4（PAK4）靶向降解药物（PpD）在肾癌免疫治疗中的潜在机制。（剩余9885字）