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

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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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          Author and article information

          Journal
          Mol Med Rep
          Molecular medicine reports
          Spandidos Publications
          1791-2997
          1791-2997
          November 1 2008
          : 1
          : 6
          Affiliations
          [1 ] Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
          Article
          10.3892/mmr_00000038
          21479494
          f475ee69-6ce1-43ef-98f5-a1b1ab34c49a
          History

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