RNA Interference Expression C1QBP Reversal Of Multidrug Resistance Of Choriocarcinoma Chemotherapy

Background and Objective:Choriocarcinoma (CC) is a highly malignent but chemotherapy sensitive solid tumor of reproductive-age women. Nowadays, chemoresistance has become the main reason leading to poor prognosis. It is greatly significant to study in its mechanism and exploit effective method to reverse drug-resistance. Autophagy is a type of cellular catabolic response to metabolic stress, involving the degradation of unfolded or aggregated proteins and damaged organelles to maintain intracellular homeostasis. Recent studies showed autophagy can facilitate cancer’s chemoresistance. The abrogation of autophagy potentiates the re-sensitization of tumor cells to chemotherapy. C1QBP is a kind of multifunctional proteins. Our previous study indicated C1QBP has a higher expression level in drug-resistant CC cell lines than sensitive CC cell lines, and induces chemoresitance through the regulation of autophagy. The silence of C1QBP could repress autophagy and reverse drug-resistance in vitro. This study attempts to find C1QBP’s relavence to protein degradation pathway especially selective autophagy and its effect in CC cell drug-resistance both in vitro and in vivo.Methods:We synthesized Lentivirus vectors expressing shRNA to infect drug resistant CC cell line Jeg3/VPC for effective C1QBP silence. Western blot was used to confirm the interfering efficiency of C1QBP. Cell counting cit (CCK-8) assay was used to monitor the change of interfered cells’IC50and resistance index (RI). We established Human CC cell nude mice xenografts and gave themMTX or VP16intraperitoneal injections, compared tumor growth rate with negative controls to establish an optimal CC chemotherapy in vivo model and than evaluated the effect of C1QBP silence in CC drug-resistance in the model. We tested the co-expression of C1QBP and selective autophagy receptor p62both in cells and xenografts.Results:We successfully synthesized C1QBP shRNA lentivirus vectors and infected VP16-resistant human CC cell line Jeg3/VPC. High C1QBP RNAi efficiency was obtained, but the interference efficiency attenuated after repeated cell subcultures. Effective silence of C1QBP obviously decrease Jeg3/VPC cells’VP16IC50and RI (P<0.05) with a decline percentage of92.86%. The xenografts of C1QBP interfered cells showed a retarded growth rate and in VP16injection group, both of the tumors’ volumn and weight suppression rate evidently increased. The silence of C1QBP up-regulated p62expression and changed its expression phenotype in in vitro culture cells. In xenograft tumor tissues, both of p62and C1QBP were tested.Conclusions:The silence of C1QBP in CC drug-resistant cell Jeg3/VPC can suppress its proliferation and reverse its drug-resistant to VP16both in vitro and in vivo. C1QBP can regulate p62expression and may play its role in chemoresistance through the regulation of selective autophagy.