RT Journal Article SR Electronic T1 Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines <em>In Vitro</em> and <em>In Vivo</em> JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 5973 OP 5982 DO 10.21873/anticanres.13802 VO 39 IS 11 A1 OGASAWARA, SACHIKO A1 MIHARA, YUTARO A1 KONDO, REIICHIRO A1 KUSANO, HIRONORI A1 AKIBA, JUN A1 YANO, HIROHISA YR 2019 UL http://ar.iiarjournals.org/content/39/11/5973.abstract AB Background/Aim: Lenvatinib is a potent inhibitor of receptor tyrosine kinases, targeting vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), KIT, and RET. Here, we investigated the antiproliferative effects of lenvatinib in liver cancer cells in vitro and in vivo. Materials and Methods: Eleven hepatocellular carcinoma cell lines and two combined hepatocellular/cholangiocarcinoma cell lines were treated with 0-30 渭M lenvatinib. Cell growth, apoptosis and the expression of FGFR1-4, FGF19, fibroblast growth factor receptor substrate (FRS)2伪 and RET were examined. Two HCC cell lines were subcutaneously implanted on nude mice and mice were treated with 3, 10, 30 mg/kg/day of lenvatinib or vehicle for 14 consecutive days. Tumor volume was measured every 3 days. Mice were sacrificed on day 15 and tumors were processed for histological examination. Blood vessels, microvessel density, necrosis, and apoptosis were also examined. Results: Lenvatinib dose- and time-dependently inhibited growth of all cell lines; however, sensitivity to lenvatinib varied. Apoptosis was not observed in any cell line, and expression of FGFR1, -2, -3 and -4, FGF19, FRS2伪, and RET were observed in these cell lines. Cell lines with high expression of these factors showed higher response to lenvatinib. In mice, lenvatinib dose-dependently suppressed tumor growth. Blood vessels and microvessel density were significantly reduced and the rate of necrosis was significantly increased by lenvatinib; apoptosis was not observed. Conclusion: Antiproliferative effects of lenvatinib on liver cancer cells were observed in vitro and in vivo. Lenvatinib may suppress tumor formation by inhibiting angiogenesis, and via an additional direct antiproliferative effect in some liver cancer cells.