We examined the anti-
tumor effect of a novel
benzoic acid derivative,
TAC-101 (4-[3,5-bis(trimethylsilyl)
benzamide]
benzoic acid) on models with liver
metastasis.
Oral administration of
TAC-101 significantly inhibited spontaneous liver
metastasis of AZ-521 (human
gastric cancer ) by orthotopic implantation to athymic nude mice. It also inhibited both the liver
metastasis of AZ-521 induced by intrasplenic injection and the secondary lung
metastasis from the liver. In addition,
TAC-101 inhibited the proliferation of Co-3 (human
colon adenocarcinoma) that formed a single nodule in the liver of athymic nude mice by intrahepatic implantation. The growth inhibitory effect of
TAC-101 on AZ-521 experimental liver
metastasis was observed when treatment was started on day 7, 14, or 21 which may correspond to the progressive stage of liver
metastasis in clinical settings. Multiple administration of
TAC-101 (8 mg/kg/day) significantly prolonged survival time of the animals with liver
metastasis by intrasplenic injection of AZ-521 (T/C = 230%) and A549 (human
lung adenocarcinoma; T/C = 186%). These effects of
TAC-101 were stronger than those of
5-FU, CDDP or ATRA. Furthermore,
TAC-101 inhibited the binding of
AP-1 to
DNA on electrophoretic mobility shift assay using nuclear extract of AZ-521 cells, although ATRA did not inhibit. These findings suggested that
TAC-101 may be a candidate for a new class of anti-
cancer agents for liver
metastasis.