Reversal of cisplatin resistance in a gastric cancer cell line by cationic liposomes loaded with signal transducer and activators of transcription 3 small interfering RNA

Abstract

Objective To investigate the effect and mechanism of the reversal of cis-platinum complexes (DDP) resistance in an gastric cancer cell line by cationic liposomes loaded with signal transducer and activators of transcription 3 (STAT3) small interfering RNA (siRNA) (STAT3/DOTAP-Lip).Methods A human gastric adenocarcinoma cell line which is resistant to DDP (SGC7901/DDP) was selected by continuous cuhure in media containing stepwise increasing concentration of DDP from 1.0 to 30.0 mg/L.Cell proliferation assays were used to determine the resistance index of SGC7901/DDP.Furthermore,STAT3/DOTAP-Lip was developed by a thin-film extrusion method (400,200,80 nm extrusion),and the size,zeta potential and encapsulation efficiency of siRNA of STAT3/DOTAP-Lip were measured.Cell transfection experiment and tumor-bearing nude mice treatment were determined to evaluate the in vitro and in vivo antitumor activity (siRNA concentration:0.5 mg/kg).Results SGC7901/DDP was successfully developed by a gradient induction method with a resistance index of 7.35.The average size of STAT3/DOTAP-Lip was (111.4 ± 9.6) nm.The encapsulation efficiency was 90.1％.The cell proliferation assay showed that STAT3/DOTAP-Lip remarkablely reversed the DDP resistance of SGC7901/DDP.Furthermore,we studied the reversal of DDP resistance in nude mice bearing SGC7901/DDP xenograft by STAT3/DOTAP-Lip.Significantly,STAT3/DOTAP-Lip combined with DDP notablely inhibited the tumor development and possessed the obvious antitumor activity compared with other groups (P ＜0.05).Conclusion STAT3/DOTAP-Lip could remarkablely reverse the DDP resistance of SGC7901/DDP both in vitro and in vivo,indicating that it could be used as an effective nanomedicine in the treatment of human gastric cancer with DDP resistance. Key words: Gastric cancer; Multidrug resistance; Cationic liposome; Chemotherapy