Cisplatin (CDDP) is a chemotherapeutic
drug that is often used for the treatment of
hepatoblastoma. However, many patients acquire resistance to therapeutic agents leading to local and distant treatment failure. It has been shown that suppression
survivin contributed to the inhibition of
tumor growth and enhanced chemotherapeutic sensitivity in several types of
cancer. The aim of the present study was to determine whether treatment with
sepantronium bromide (
YM155), a novel small molecule inhibitor of
survivin, enhanced the sensitivity of CDDP to
hepatoblastoma cells, leading to the therapeutic efficacy of
cisplatin. In vitro and in vivo models were used to examine the anticancer efficacy of
YM155, either as a monotherapy or in combination with CDDP to identify more effective
therapeutics against
hepatoblastoma. The results showed that
survivin expression was upregulated in
hepatoblastoma tissues and cell lines, and that
YM155 inhibited
survivin expression in
hepatoblastoma cells in a dose-dependent manner.
YM155 enhanced sensitivity of CDDP to human HepG2 and HuH-6
hepatoblastoma cells. The
YM155 combination with CDDP in
hepatoblastoma cells significantly decreased cell proliferation and formation, and induced cell apoptosis than either agent alone. In a mouse xenograft model,
YM155 combined with CDDP significantly suppressed
tumor growth compared to the monotherapy. Taken together, these findings suggested that the combination of
YM155 and CDDP is a promising
drug candidate for the treatment of
hepatoblastoma.