J Cancer 2022; 13(5):1603-1610. doi:10.7150/jca.68169 This issue

Research Paper

Tranexamic acid reduces endometrial cancer effects through the production of angiostatin

Keiichi Hiramoto, Yurika Yamate

Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan

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Citation:
Hiramoto K, Yamate Y. Tranexamic acid reduces endometrial cancer effects through the production of angiostatin. J Cancer 2022; 13(5):1603-1610. doi:10.7150/jca.68169. Available from https://www.jcancer.org/v13p1603.htm

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Abstract

Graphic abstract

Tranexamic acid (TA) has been reported to exhibit antitumor effects in various mouse models of cancer. However, the mechanism underlying its antitumor effects against endometrial cancer remains to be elucidated. This study was aimed at investigating the efficacy of TA against chronic inflammation-associated endometrial cancer induced by N-methyl-N-nitrosourea (MNU) and estradiol in a mouse model. After cancer induction, the mice were administered TA (12 mg/kg) three times weekly during the experimental period. The endometrial cancer development induced by MNU and estradiol was ameliorated by TA administration. Furthermore, TA treatment suppressed the levels of carbohydrate antigen 125, interleukin-6, and tumor necrosis factor-α in the plasma. The level of plasminogen, known as a TA target, increased in endometrial cancer and was further increased by TA treatment. On the other hand, plasmin levels increased in the model mice but decreased after TA treatment. Furthermore, the macrophage counts and the levels of matrix metalloproteinase (MMP)-12 and angiostatin in tumor cells in the uterus increased compared to the corresponding values in the control group and further increased upon TA treatment. The results of our study indicate that TA ameliorated the endometrial cancer induced by MNU and estradiol by regulating the macrophage/MMP-12/plasminogen/angiostatin signal transmission pathway.

Keywords: Tranexamic acid, Endometrial cancer, Plasminogen, Macrophages, Angiostatin