Therapeutic effect of clarithromycin on a transplanted tumor in rats

The therapeutic antitumor effect of clarithromycin (CAM) was examined with the 13762NF mammary adenocarcinoma and F-344 rat system. When CAM treatment at a dosage of 2 mg/kg of body weight orally for 21 days was commenced aft er inoculation of the tumor, no significant decrease in death rate was obse rved, although the loss in body weight was less than that in the untreated group. When tumor-bearing (TB) rats were treated with CAM in combination wi th carboplatin or cylophosphamide, a significant decrease in the death rate was obtained, although neither treatment alone proved to be effective. A b eneficial effect was also observed when CAM treatment was combined with sur gical treatment. CAM showed no direct cytotoxicity to this tumor in vitro a ccording to the MTT (3-[4,5-dimethylthiazol-2-y]-2,5-diphenyltetrazolium br omide) assay. Spleen cells obtained from TB rats receiving CAM treatment sh owed a stronger tumor-neutralizing activity than those from rats which had not received CAM treatment (Winn assay). Enhanced induction of cytotoxic ce lls to allogeneic tumor was also observed in rats immunized with allogeneic tumor cells together with CAM treatment (Cr-51 release assay). The 13762NF tumor produces transforming growth factor-beta (TGF-beta), tumor necrosis factor alpha, and matrix metalloproteinase 9, and treatment of tumor cells with CAM in vitro for 24 h significantly inhibited the expression of the ge nes coding for these proteins (reverse transcription-PCR). Levels of expres sion of the TGF-beta and interleukin-6 genes of spleen cells obtained from CAM-treated TB rats were both significantly lower than those of spleen cell s from CAM-untreated TB rats. This study suggests that CAM has biological r esponse modifier activities resulting in a beneficial therapeutic antitumor effect and might be useful for the treatment of human cancers.