FL118 a novel survivin inhibitor wins the battle against drug-resistant and metastatic lung cancers through inhibition of cancer stem cell-like properties

摘要

Failure of cancer treatment caused by drug resistance and metastasis is mainly due to existence of cancer stem cells (CSCs). Therefore, targeting CSCs to overcome cancers is a challenging issue in clinic. In this report, in view of the important role of survivin in tumor growth and CSCs maintaining, we aimed to confirm that FL118, as a novel survivin inhibitor, may effectively inhibit lung cancer stem cells. We showed that lung cancer stem cells have the obviously higher expression of survivin than their parental cells. After treated with FL118, the survivin level in CSCs was suppressed. Consistently, lung cancer stem cells displayed significantly growth inhibition over time. Here, we compared the antitumor efficacy between FL118 and cisplatin. The data revealed that CSCs are more sensitive to FL118 than cisplatin. To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells. Moreover, FL118 effectively decreased the invasive ability of CSCs. These findings expand the uniqueness of FL118 as an attractive therapeutic option for cancers with drug-resistant or metastatic potential.