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ID 115035
Author
Lila, Amr S. Abu Tokushima University|Zagazig University|Hail University
Moriyoshi, Naoto Tokushima University
Fukushima, Masakazu Tokushima University
Huang, Cheng-Long Kyoto University
Wada, Hiromi Kyoto University
Keywords
Colorectal cancer
PEG-coated shRNA-lipoplex
RNAi
S-1
Short hairpin RNA
Thymidylate synthase
Content Type
Journal Article
Description
Metronomic chemotherapy is currently considered an emerging therapeutic option in clinical oncology. S-1, an oral formulation of Tegafur (TF), a prodrug of 5-fluorouracil (5-FU), is designed to improve the antitumor activity of 5-FU in tandem with reducing its toxicity. Clinically, metronomic S-1 dosing has been approved for the standard first- and second-line treatment of metastatic or advanced stage of colorectal (CRC). However, expression of intratumor thymidylate synthase (TS), a significant gene in cellular proliferation, is associated with poor outcome to 5-FU-based chemotherapeutic regimens. In this study, therefore, we examined the effect of a combination of TS silencing by an RNA interfering molecule, chemically synthesized short hairpin RNA against TS (shTS), and 5-FU on the growth of human colorectal cancer cell (DLD-1) both in vitro and in vivo. The combined treatment of both shTS with 5-FU substantially inhibited cell proliferation in vitro. For in vivo treatments, the combined treatment of metronomic S-1 dosing with intravenously injected polyethylene glycol (PEG)-coated shTS-lipoplex significantly suppressed tumor growth, compared to a single treatment of either S-1 or PEG-coated shTS-lipoplex. In addition, the combined treatment increased the proportion of apoptotic cells in the DLD-1 tumor tissue. Our results suggest that metronomic S-1 dosing combined with TS silencing might represent an emerging therapeutic strategy for the treatment of patients with advanced CRC.
Journal Title
Cancer Letters
ISSN
03043835
NCID
AA00598513
AA1152274X
Publisher
Elsevier
Volume
400
Start Page
223
End Page
231
Published Date
2016-11-09
Rights
© 2016 The Author(s). Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version)
URL ( Publisher's Version )
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language
eng
TextVersion
Publisher
departments
Pharmaceutical Sciences