We determined the Flavopiridol in vivo effect of silencing MDR1 expression by ultrasound microbubble-mediated siRNA delivery on multidrug resistance of yolk sac carcinamo cells. P-glycoprotein encoded

by MDR1 gene is in charge of decreasing drug accumulation in multidrug-resistant cells, including tumor cells. Daunorubicin is used in cancer chemotherapy and its subcellular distribution is related to multidrug resistance. Daunorubicin produces red fluorescence with laser excitation at 488 nm, which is readily detected in drug-treated tissues or cells. Thus, Daunorubicin accumulation assay was LXH254 in vitro performed to detect P-glycoprotein activity. Our results indicated that ultrasound microbubble-mediated delivery effectively transferred siMDR1 into L2-RYC cells and led to an increased Daunorubicin accumulation. Chemotherapeutic drugs are means to combat cancers clinically. However, drug-resistance of tumor cells severely limits therapeutic

outcomes. Drug sensitivity can be estimated by tumor cell viability treated with anti-cancer drug. Vincristine and Dactinomycin both of which are most commonly used chemo drugs and also known as substrates of P-glycoprotein. Thus, MTT assay was carried out to detect cell viability HM781-36B cell line at different concentrations of Vincristine and Dactinomycin and to determine the IC50 ratios of two drugs in each group. Our results revealed that the L2-RYC cells treated with ultrasound microbubble-mediated siMDR1

delivery became more sensitive to anti-cancer drugs. Conceivably, silencing MDR1 should achieve excellent therapeutic efficacy at lower drug dosages so that chemotherapy-associated side effects can be alleviated to certain extends. Conclusions In this study, we constructed plasmids expressing siMDR1 and confirmed their silencing efficiency in L2-RYC cells. Ultrasound microbubble-mediated delivery can effectively transfer siMDR1 into L2-RYC cells and lead to inhibition Nintedanib (BIBF 1120) of MDR1 expression and function of P-glycoprotein. Drug sensitivity was also improved by silencing MDR1. Thus, ultrasound microbubble-mediated delivery approach is a safe and effective gene transfection method and targeted inhibition method. Our results strongly suggested that combined gene silencing and chemotherapy may be further explored as a novel and potentially efficacious treatment of yolk sac carcinoma. Acknowledgements We thank the editors and reviewers for their valuable comments and suggestions which are helpful for improving this manuscript. This work was supported by a research grant from the National Natural Science Foundation of China (No.81001030). Electronic supplementary material Additional file 1: Supplementary Figure 1. Map of pSEB-HUS vector and schematic diagram of recombination. (JPEG 487 KB) Additional file 2: Supplemental table 1. siRNA targeting MDR1 and PCR primer oligonucleotide sequence. (DOC 34 KB) References 1.