Combination therapy of tyrosine kinase receptor inhibitor TSU-68 (SU6668) and paclitaxel inhibits subcutaneous xenografts of endometrial cancer

被引:6
|
作者
Machida, Shizuo [1 ]
Saga, Yasushi [1 ]
Takei, Yuji [1 ]
Takahashi, Kayoko [1 ]
Nonaka, Hiroaki [1 ]
Fujiwara, Hiroyuki [1 ]
Ohwada, Michitaka [1 ]
Suzuki, Mitsuaki [1 ]
机构
[1] Jichi Med Univ, Jichi Med Sch, Dept Obstet & Gynecol, Shimotsuke, Tochigi 3290498, Japan
关键词
TSU-68; paclitaxel; endometrial cancer; angiogenesis; HEC1A;
D O I
10.3892/mmr_00000038
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
TSU-68 is a small-molecular-weight synthetic inhibitor of the tyrosine kinase receptors Flk-1/KDR, PDGFRB 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.
引用
收藏
页码:843 / 846
页数:4
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