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

  • Authors:
    • Shizuo Machida
    • Yasushi Saga
    • Yuji Takei
    • Kayoko Takahashi
    • Hiroaki Nonaka
    • Hiroyuki Fujiwara
    • Michitaka Ohwada
    • Mitsuaki Suzuki
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/mmr_00000038
  • Pages: 843-846
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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.

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November 2008
Volume 1 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Machida, S., Saga, Y., Takei, Y., Takahashi, K., Nonaka, H., Fujiwara, H. ... Suzuki, M. (2008). Combination therapy of tyrosine kinase receptor inhibitor TSU-68 (SU6668) and paclitaxel inhibits subcutaneous xenografts of endometrial cancer. Molecular Medicine Reports, 1, 843-846. https://doi.org/10.3892/mmr_00000038
MLA
Machida, S., Saga, Y., Takei, Y., Takahashi, K., Nonaka, H., Fujiwara, H., Ohwada, M., Suzuki, M."Combination therapy of tyrosine kinase receptor inhibitor TSU-68 (SU6668) and paclitaxel inhibits subcutaneous xenografts of endometrial cancer". Molecular Medicine Reports 1.6 (2008): 843-846.
Chicago
Machida, S., Saga, Y., Takei, Y., Takahashi, K., Nonaka, H., Fujiwara, H., Ohwada, M., Suzuki, M."Combination therapy of tyrosine kinase receptor inhibitor TSU-68 (SU6668) and paclitaxel inhibits subcutaneous xenografts of endometrial cancer". Molecular Medicine Reports 1, no. 6 (2008): 843-846. https://doi.org/10.3892/mmr_00000038