Ribonucleotide reductase M2 is a promising molecular target for the treatment of oral squamous cell carcinoma

Iwamoto,Kazuki; Nakashiro,Koh-Ichi; Tanaka,Hiroshi; Tokuzen,Norihiko; Hamakawa,Hiroyuki

doi:10.3892/ijo.2015.2912

Ribonucleotide reductase M2 is a promising molecular target for the treatment of oral squamous cell carcinoma

Authors:
- Kazuki Iwamoto
- Koh-Ichi Nakashiro
- Hiroshi Tanaka
- Norihiko Tokuzen
- Hiroyuki Hamakawa
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Affiliations: Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
Published online on: March 2, 2015 https://doi.org/10.3892/ijo.2015.2912
Pages: 1971-1977

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Abstract

In our previous study, ribonucleotide reductase M2 (RRM2) was identified as a cancer-related gene commonly overexpressed in human oral squamous cell carcinoma (OSCC) cell lines. Herein, we attempted to determine whether targeting RRM2 may be a plausible therapeutic approach for the treatment of patients with OSCC. First, we examined the expression levels of RRM2 in human OSCC cell lines and tissues. Overexpression of RRM2 in OSCC was confirmed by western blot analysis. Subsequently, we investigated the effects of a synthetic small interfering RNA specific for RRM2 and gemcitabine (GEM), an inhibitor of RRM2 enzymatic activity, on the growth of human OSCC cell lines and primary cultured cells. Targeting RRM2 by RNA interference almost completely suppressed the expression of RRM2 and markedly suppressed the growth of both types of cells by >54.8%. GEM also reduced the growth rate of these cells by >83.0%. Finally, we evaluated the antitumor effects of GEM, cisplatin (CDDP), 5-fluorouracil (5-FU), and docetaxel (DOC) against OSCC cells using the collagen gel droplet embedded culture drug sensitivity test. OSCC cells were more sensitive to GEM and DOC than to CDDP and 5-FU, regardless of the expression level of RRM2 mRNA. These results suggested that RRM2 supported the growth of human OSCC cells and that targeting of RRM2, e.g., via GEM treatment, may be a promising therapeutic strategy for OSCC.

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