[Therapeutic effects of C-erbB-2 and C-raf-1 gene combined with antisense oligodeoxynucleotide on the human ovarian carcinoma transplanted subcutaneously in nude mice].

BACKGROUND & OBJECTIVE: Although many positive studies were reported on single C-erbB-2 or C-raf-1 antisense oligodeoxynucleo- tide (ASODN) in cancer treatment, these studies were usually limited in single gene or in cell level and were not appropriate according to the multiple genes hypotheses of tumorigenesis. This study was designed to investigate the effects of C-erbB-2 and C-raf-1 combined with ASODN on the treatment of ovarian carcinoma xenograft in nude mice.

METHODS

The model of xenografts derived from ovarian epithelial cancer SKOV3 cells was established in Balb/C nude mice, then they were randomly divided into a negative control group and 6 experimental groups [intraperitoneal injection of (1)liposome-C-erbB-2-ASODN, (2)liposome- C-raf-1-ASODN, (3)liposome-C-erbB-2-ASODN, (4)liposome-C-raf-1-ASODN, (5)whole-dose combined ASODN, (6)half-dose combined ASODN. The weight of nude mice and tumor volume were measured. The tumor growth inhibitory rates and the tumor volume decreased rates were calculated.

RESULTS

C-erbB-2 and C-raf-1 combined with ASODN exhibited potent tumor growth inhibition. The tumor volume inhibitory rates were 72.5% and 78.4%; the tumor weight inhibitory rates were 70.7% and 75.3%; the tumor volume decreased rates were 29.7% and 41.6% for whole-dose combined group and half-dose combined group post-experiment, respectively. Of the 7 groups, there was no significant difference on nude mice weight post-experiment and therefore the toxicity was endurable.

CONCLUSION

C-erbB-2 and C-raf-1 combined with ASODN showed potent tumor growth inhibition in vivo.