The Study Of Cisplatin-loaded Human Mesenchymal Stem Cells Derived Exosomes Inhibit Epithelial Ovarian Cancer Growth In Vitro

Background and objective: Epithelial ovarian cancer(EOC)is one of the most harmful malignant tumors in women.In the current clinical treatment in China,the traditional chemotherapeutic regimen is the most common adjuvant therapy choice.However,the clinical status indicates that platinum chemotherapy has two obvious disadvantages in treating epithelial ovarian cancer: drug toxicity and resistance.These problems interfere with the positive effects of normal treatment and prevent patients from getting the optimal benefit of treatment.In the past decade,exosomes derived mesenchymal stem cells are a novel and safe drug carrier for cancer treatment,which can be combined with traditional therapies and show good effects in cancer treatment.The purpose of this study is to combine cisplatin with exosome to prepare a new nano-drug,observe its effect on the growth of epithelial ovarian cancer cell line A2780,and study the anticancer effect of cisplatin loaded exosome.Methods: Mesenchymal stem cells were isolated and cultured from umbilical cord tissue.Exosomes were collected from serum-free supernatant of mesenchymal stem cells.After that,cisplatin was loaded into exosomes by ultrasonic technology.And the structure and function of the drug-loading exosomes were evaluated by transmission electron microscopy,protein western blot,nano-particle tracking analysis,and laser confocal microscopy.The drug loading rate was analyzed of exosomes by ultra-performance liquid chromatography quadrupole time of flight mass spectrometer.Finally,epithelial ovarian cancer cell line A2780 was treated with cisplatin-loaded exosomes,and the cells were collected for cytotoxicity test,cell proliferation test,cell apoptosis test,Transwell invasion test,and wound-healing assay.These results can evaluate the effects of cisplatin-loaded exosomes on tumor growth indexes such as cell proliferation,migration,and invasion of epithelial ovarian cancer cells in vitro.Results: The structure and function of exosomes did not change after ultrasonic treatment.And the drug loading rate was up to 9.29%.After drug treatment,the concentration of cisplatin alone of epithelial ovarian cancer cell line A2780 was 67.33 fold higher than that cisplatin in the exosome-DDP under similar cytotoxicity results.Exosomes-DDP could effectively inhibit the viability and proliferation of cancer cells and induce apoptosis of cancer cells.At the same time,exosomes-DDP also had good performance in the invasion and migration of cancer cells and could effectively inhibit them.Conclusions: In vitro studies have confirmed that cisplatin can be successfully loaded into exosomes and has an anti-ovarian cancer effect.Exosomes-DDP can greatly reduce the dosage of cisplatin,which indicates that it is expected to reduce the dosage of platinum drugs in clinical practice in the future,improve drug toxicity and solve problems such as platinum drug resistance.