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 after inoculation of the
tumor, no significant decrease in death rate was observed, 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 with
carboplatin or
cyclophosphamide, a significant decrease in the death rate was obtained, although neither treatment alone proved to be effective. A beneficial effect was also observed when CAM treatment was combined with surgical treatment. CAM showed no direct cytotoxicity to this
tumor in vitro according to the MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
bromide) assay. Spleen cells obtained from TB rats receiving CAM treatment showed a stronger
tumor-neutralizing activity than those from rats which had not received CAM treatment (Winn assay). Enhanced induction of cytotoxic cells to allogeneic
tumor was also observed in rats immunized with allogeneic
tumor cells together with CAM treatment (51Cr 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 genes coding for these
proteins (reverse transcription-PCR). Levels of expression 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 cells from CAM-untreated TB rats. This study suggests that CAM has
biological response modifier activities resulting in a beneficial therapeutic antitumor effect and might be useful for the treatment of human
cancers.