[Experimental studies on anti-mouse hepatocellular carcinoma effects of cisplatin combined with exosomes].
OBJECTIVE
To study the anti-tumor effects and mechanisms of cisplatin(DDP) combined with exosomes.


METHODS
The cell-growth inhibition of DDP on H(22); cells was analyzed by MTT assay.The mice were immunized by H(22); cell-derived exosomes. The exosomes elicited CTL-specific cytotoxicity and DDP enhanced cytotoxicity in combination with CTL were detected by (3)H-TdR release assay. The effect of DDP on mRNA and protein levels of Fas in H(22); was analyzed using RT-PCR and Western blot.The expression of FasL on spleen lymphocyte was determined by RT-PCR. BALB/c mice inoculated with hepatoma carcinoma cell line H(22); were used as tumor models.The mice received exosomes solely or in combination with DDP.The survival of the mice was observed.


RESULTS
DDP inhibited H(22); cell in a dose-dependant manner. The exosomes elicited CTL-specific cytotoxicity was enhanced by DDP (P<0.05). RT-PCR and Western blot showed Fas increased gradually after administering DDP on H(22); cells.RT-PCR also indicated the mRNA level of FasL on mice spleen lymphocyte increased after immunized by exosomes. Compared with other groups, the combination group(DDP plus exosomes)could statistically prolong the survival time (P<0.05).


CONCLUSIONS
The therapy of DDP combined with exosomes had significant synergistic effect against tumor. The mechanism of synergistic effect includes enhancement of CTL activity.
Wang
Shao-Hua
SH
Department of Pathophsiology, Institute of Stem Cell and Tissue Engineering, Chongqing Medical University, China. wangshaohua20006@163.com
Shen
Yi
Y
Li
Jing
J
Xiang
Zi-Wu
ZW
Fan
Wei-Ke
WK
Chen
Li
L
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D055354:Exosomes / Q000276:immunology*; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D019014:fas Receptor; D002945:Cisplatin