Rivaroxaban does not affect growth of human pancreatic tumors in mice

Abstract

Background Some clinical studies have shown that low‐molecular‐weight heparins (LMWHs) prolong the survival of cancer patients. In addition, various anticoagulants have been shown to reduce growth of tumors in mice. However, there are no studies on the effect of the factor Xa inhibitor rivaroxaban on growth of human pancreatic tumors in nude mice. Objectives To test the hypothesis that the factor Xa inhibitor rivaroxaban reduces the growth of tissue factor (TF)‐positive pancreatic tumors but not TF‐negative pancreatic tumors in mice. Methods The TF‐positive human pancreatic cancer cell line BxPc‐3 and the TF‐negative human pancreatic cancer cell line MIA PaCa‐2 were injected subcutaneously into nude mice and tumors grown to a mean volume of ~100 mm3. Mice were then divided into two groups. One group was fed chow containing rivaroxaban (0.5 g/kg chow) whereas the other group was fed chow without rivaroxaban. Results Rivaroxaban significantly prolonged prothrombin time in tumor‐bearing mice. Rivaroxaban did not affect cell proliferation or growth of either BxPc‐3 or MIA PaCa‐2 tumors grown subcutaneously in nude mice. Conclusion Our results indicate that inhibition of factor Xa with rivaroxaban does not affect the growth of two human pancreatic tumors in nude mice.

A systematic review on the effects of direct oral anticoagulants on cancer growth and metastasis in animal models

“…Next, they extended their findings to BxPc-3, a pancreatic cancer cell line that is positive for the transmembrane protein TF, the initiator of coagulation [33]. In line with the findings using Mia PaCa-2 cells, rivaroxaban treatment neither affected tumor growth nor proliferation of BxPc-3 cells [25].…”

“…Subsequently, full-text version of all abstracts were retrieved to assess whether inclusion criteria were met for inclusion in the qualitative assessment. To include also the most recent studies, the search strategy was repeated in PubMed and EMBASE on the 7th of October 2019, yielding three additional records with a publication date in 2019 [23][24][25].…”

“…n.descr., not described in paper; no., number; i.p., intraperitoneal; i.v., intravenous; s.c., subcutaneous. [29][30][31][32], two studies reported on rivaroxaban (both 2019) [24,25], and one study reported on both dabigatran etexilate and rivaroxaban (2019) [23].…”

“…The 9 selected publications included a total of 19 in vivo experiments (Table 1). Experiments were conducted in mice (n = 18) or rats (n = 1) of both male and female sex; and included carcinogenicity studies [28], spontaneous breast cancer [24], subcutaneous (fibrosarcoma [24], colorectal [24] and pancreatic cancer [25]), orthotopic (pancreatic [28,32] and breast cancer [29,31,23]) and experimental metastasis models (melanoma [27] and ovarian cancer [30]). The number of animals per treatment group ranged from 4 to 50.…”

“…Maqsood et al used a xenograft model in which 2 × 10 6 human MIA PaCa-2 pancreatic cancer cells were s.c. injected into immunocompromised nude mice [25]. Treatment with rivaroxaban (0.5 mg/g chow diet) was started when tumor size reached 100 mm 3 , but tumor growth was not affected as assessed by tumor weight, nor did it affect proliferation of tumor cells as determined by the percentage Ki-67-positive tumor cells [25]. Next, they extended their findings to BxPc-3, a pancreatic cancer cell line that is positive for the transmembrane protein TF, the initiator of coagulation [33].…”