title: Combination therapy of tyrosine kinase receptor inhibitor TSU-68 (SU6668) and paclitaxel inhibits subcutaneous xenografts of endometrial cancer.
abstract: TSU-68 is a small-molecular-weight synthetic inhibitor of the tyrosine kinase receptors Flk-1/KDR, PDGFRβ and FGFR1, which are involved in angiogenesis. Using a mouse model in which endometrial cancer was subcutaneously implanted, we investigated the effects of TSU-68 alone or in combination with paclitaxel. We subcutaneously implanted a cell strain of endometrial cancer, HEC1A, into BALB/c nude mice. TSU-68 was orally administered every day, while paclitaxel was intraperitoneally injected once a week, and the rates of subcutaneous tumor proliferation were compared. In a group treated with high-dose (200 mg/kg/day) TSU-68 alone, subcutaneous tumor proliferation was significantly inhibited in comparison with a vehicle-treated control group (p<0.05). In groups treated with low-dose TSU-68 or paclitaxel alone (100 and 10 mg/kg/day, respectively), tumor proliferation was not significantly inhibited. In a low-dose combination therapy group (100 mg/kg/day of TSU-68 + 10 mg/kg/day of paclitaxel), tumor proliferation was significantly inhibited in comparison with the control and low-dose TSU-68 or paclitaxel therapy groups (p<0.01). High-dose monotherapy with TSU-68 inhibited the proliferation of the subcutaneously implanted tumor. Furthermore, a combination of TSU-68 and paclitaxel at a low dose, one at which respective monotherapy was not effective, inhibited tumor proliferation. Combination therapy with the two agents may therefore be useful for treating endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Machida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saga
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takei
authors.forename: Kayoko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nonaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ohwada
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki