[Enhancement of antitumor effect of cisplatin on human ovarian cancer by cyclosporin A in vitro and in vivo].
OBJECTIVE
To investigate the enhanced impact of cyclosporin A (CsA) on antitumor activity of cisplatin (DDP) for human ovarian cancer cells.


METHODS



METHODS
human ovarian adenocarcinoma cells (COC1) and its resistant subline (COC1/DDP) were cultured separately with 4 different preparations: (1) normal saline; (2) CsA alone; (3) DDP alone; (4) DDP plus CsA. After 72 hours, the numbers of tumor cells were counted under microscope. Furthermore, 3H-thymidine incorporation tests were performed on the above 4 systems, and the inhibitory rate of tumor growth were calculated. In vivo studies: normal saline or 2mg/kg of DDP and 5mg/kg of CsA was injected intraperitoneally to nude mice with COC1/DDP xenograft cancer every 3 day for 3 times. The changes of tumor volumes and its pathological appearances were compared before and after treatment.


RESULTS
IN VITRO STUDIES, DDP combined with CsA exhibited a synergistic cytotoxic effect on COC1 and COC1/DDP cells. The decrease of tumor cell numbers reached 24%-36%, 48%-60% of controls respectively. The inhibitory rates of DNA synthesis of these tumor cells, measured by 3H-TdR incorporation tests, were greater in DDP plus CsA group than those in DDP alone group (64.7% 63.9% versus 39.6% 25.1%, P < 0.01). The greater inhibitory rates of CsA+DDP regimen (81.4%) was also shown in vivo studies when compared with DDP alone regimen (49.1%) (P < 0.01). There were significant decreases of tumor cell density and nuclear mitosis in the combined group as compared with that of the DDP alone group (P < 0.01).


CONCLUSIONS
The combination of DDP with 2 micrograms/ml of CsA yields enhancement of antitumor effect on human ovarian cancer. This study suggests that CsA may be used clinically as an antitumor enhancement of DDP for the treatment of ovarian adenocarcinoma.
Zhou
Y
Y
Beijing Railway General Hospital.
Chen
H
H
Yang
Q
Q
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D016572:Cyclosporine; D002945:Cisplatin