Assessment of anti-cancer effects for nucleoside analogues by using drug response for human mononuclear lymphocytes in vitro.

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It has been reported that nucleoside analogue such as gemcitabine (GEM) showed potent anti-tumor effects in patients with the tumor tissue expressing high levels of SLC29A1, a nucleoside transporter. We examined whether or not peripheral mononuclear leucocytes (PBMC) can be used as an alternative tissue to assess the expression levels of SLC29A1.Single nucleotide polymorphisms for SLC29A1 (rs6932345) affected the mRNA expression on PBMC, where the wild-type showed 1.7 times higher levels compared with mutation carries. Inhibitory effects of GEM on PBMC proliferation was also enhanced in the wild type. Pre-treatment of PBMC with SLC29A1 inhibitors reduced inhibitory effects of GEM on PBMC proliferation. These results suggested that PBMC could be used to assess anti-tumor effects of GEM via SLC29A1.