RT Journal Article
SR Electronic
T1 4-Methylumbelliferone Decreases the Hyaluronan-rich Extracellular Matrix and Increases the Effectiveness of 5-Fluorouracil
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 5799
OP 5804
DO 10.21873/anticanres.12919
VO 38
IS 10
A1 YOSHIDA, ERI
A1 KUDO, DAISUKE
A1 NAGASE, HAYATO
A1 SUTO, AKIKO
A1 SHIMODA, HIROSHI
A1 SUTO, SHINICHIRO
A1 KAKIZAKI, IKUKO
A1 ENDO, MASAHIKO
A1 HAKAMADA, KENICHI
YR 2018
UL http://ar.iiarjournals.org/content/38/10/5799.abstract
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.