Treatment of false-negative metastatic lymph nodes by a lymphatic drug delivery system with 5-fluorouracil

Honoka Fujii, Sachiko Horie, Ariunbuyan Sukhbaatar, Radhika Mishra, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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9 Citations (Scopus)


Metastatic lymph nodes (LNs) may be the origin of systemic metastases. It will be important to develop a strategy that prevents systemic metastasis by treating these LNs at an early stage. False-negative metastatic LNs, which are found during the early stage of metastasis development, are those that contain tumor cells but have a size and shape similar to LNs that do not host tumor cells. Here, we show that 5-fluorouracil (5-FU), delivered by means of a novel lymphatic drug delivery system (LDDS), can treat LNs with false-negative metastases in a mouse model. The effects of 5-FU on four cell lines were investigated using in vitro cytotoxicity and cell survival assays. The therapeutic effects of LDDS-administered 5-FU on false-negative metastatic LNs were evaluated using bioluminescence imaging, high-frequency ultrasound (US), and histology in MHX10/Mo-lpr/lpr mice. These experimental animals develop LNs that are similar in size to human LNs. We found that all cell lines showed sensitivity to 5-FU in the in vitro assays. Furthermore, a concentration-dependent effect of 5-FU to inhibit tumor growth was observed in tumor cells with low invasive growth characteristics, although a significant reduction in metastatic LN volume was not detected in MHX10/Mo-lpr/lpr mice. Adverse effects of 5-FU were not detected. 5-Fluorouracil administration with a LDDS is an effective treatment method for false-negative metastatic LNs. We anticipate that the delivery of anticancer drugs by a LDDS will be of great benefit in the prevention and treatment of cancer metastasis via LNs.

Original languageEnglish
Pages (from-to)2241-2251
Number of pages11
JournalCancer Medicine
Issue number5
Publication statusPublished - 2019 May


  • false-negative
  • fluorouracil (5-FU)
  • lymph node
  • lymphatic drug delivery system
  • metastasis
  • mouse


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