PT  - JOURNAL ARTICLE
AU  - YOSHIDA, ERI
AU  - KUDO, DAISUKE
AU  - NAGASE, HAYATO
AU  - SUTO, AKIKO
AU  - SHIMODA, HIROSHI
AU  - SUTO, SHINICHIRO
AU  - KAKIZAKI, IKUKO
AU  - ENDO, MASAHIKO
AU  - HAKAMADA, KENICHI
TI  - 4-Methylumbelliferone Decreases the Hyaluronan-rich Extracellular Matrix and Increases the Effectiveness of 5-Fluorouracil
AID  - 10.21873/anticanres.12919
DP  - 2018 Oct 01
TA  - Anticancer Research
PG  - 5799--5804
VI  - 38
IP  - 10
4099  - http://ar.iiarjournals.org/content/38/10/5799.short
4100  - http://ar.iiarjournals.org/content/38/10/5799.full
SO  - Anticancer Res2018 Oct 01; 38
AB  - Background/Aim: Pancreatic cancer responds poorly to most chemotherapeutic agents. Several studies have reported that hyaluronan (HA)-rich extracellular matrix (ECM) is a biological barrier against chemotherapeutic agents. 4-methylumbelliforone (MU) led to inhibition of HA synthesis and its preservation in ECM, which may enhance 5-fluorouracil (5-FU) cytotoxicity. Thus, new therapy with MU and 5-FU may be developed for pancreatic cancer. Materials and Methods: A 5-fluorouracil (5-FU) concentration and 4-methylumbelliferone (MU) dosage was analyzed by high-performance liquid chromatography (HPLC). Change in antitumor efficacy of 5-FU in combination with MU was also examined in vivo and in vitro. Results: Combined 5-FU and MU treatment inhibited cell proliferation better than 5-FU alone; 0.01 mM 5-FU alone decreased cell proliferation by 37.7 %, while 0.01 mM 5-FU with 0.5 mM MU decreased cell proliferation by 57.4%. MU enhanced the intracellular concentration of 5-FU by 47.3% compared to control. Mice tumors treated with 5-FU and MU decreased in size and animal survival was prolonged. Moreover, MU decreased cohesiveness of the intercellular space. Conclusion: Combination therapy of 5-FU with MU was effective. A novel therapy can be designed for pancreatic cancer by using ECM modulation.