Combination effect of AC-7700, a novel combretastatin A-4 derivative, and cisplatin against murine and human tumors in vivo.
The in vivo combination effect of AC-7700, a novel combretastatin A-4 derivative, and cisplatin (CDDP) was examined. The combination of AC-7700 and CDDP increased antitumor activity against murine colon 26 tumor in mice and cured the mice. This combination effect was found over wide dosage ranges of AC-7700 (20-80 mg/kg) and CDDP (2.5-5 mg/kg). Moreover, this combination augmented antitumor activity against murine S180 and M109 tumors, and human LX-1 and LS180 tumor xenografts in mice. The effect was the strongest when AC-7700 and CDDP were administered simultaneously. To study this combination effect, we measured the concentrations of CDDP in tumors, plasma and kidneys of the mice with colon 26 tumor. In the combination with AC-7700, the concentration of CDDP in the tumors increased from 0.5 to 96 h after administration, but did not change or decrease in plasma or kidneys. Against human LS180 xenografts in mice, the combination similarly increased the concentration of CDDP in the tumors. These results suggest that AC-7700 may specifically augment the accumulation of CDDP in tumors, and thus has the potential to be useful in combination chemotherapy with CDDP.
Morinaga
Yoshihiro
Y
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681. yoshihiro_morinaga@ajinomoto.com
Suga
Yasuyo
Y
Ehara
Sumiko
S
Harada
Katsuhiro
K
Nihei
Yukio
Y
Suzuki
Manabu
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D012510:Sarcoma 180 / Q000188:drug therapy*; D012694:Serine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D012694:Serine; C400245:AC 7700; D002945:Cisplatin