AIM: 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). CONCLUSION: The therapy of DDP combined with exosomes had significant synergistic effect against tumor. The mechanism of synergistic effect includes enhancement of CTL activity.
AIM: 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). CONCLUSION: The therapy of DDP combined with exosomes had significant synergistic effect against tumor. The mechanism of synergistic effect includes enhancement of CTL activity.