Son preference has persisted in the face of sweeping change these incentives without more direct efforts by economic and social changes in China, India, and the the state and civil society to increase the flexibility of the Republic of Korea. The authors attribute this to their kinship system such that daughters and sons can be similar family systems, which generate strong perceived as being more equally valuable. Much can be disincentives to raise daughters while valuing adult done to this end through social movements, legislation, women's contributions to the household. Urbanization, and the mass media. female education, and employment can only slowly

Son preference has persisted in the face of sweeping change these incentives without more direct efforts by economic and social changes in China, India, and the the state and civil society to increase the flexibility of the Republic of Korea. The authors attribute this to their kinship system such that daughters and sons can be similar family systems, which generate strong perceived as being more equally valuable. Much can be disincentives to raise daughters while valuing adult done to this end through social movements, legislation, women's contributions to the household. Urbanization, and the mass media. female education, and employment can only slowly

Paclitaxel is clinically used as a first-line chemotherapeutic regimen for several cancer types, including head and neck cancers. However, acquired drug resistance results in the failure of therapy, metastasis and relapse. The drug efflux mediated by ATP-binding cassette (ABC) transporters and the survival signals activated by forkhead box (FOX) molecules are critical in the development of paclitaxel drug resistance. Whether FOX molecules promote paclitaxel resistance through drug efflux remains unknown. In this study, we developed several types of paclitaxel-resistant (TR) nasopharyngeal carcinoma (NPC) cells. These TR NPC cells acquired cancer stem cell (CSC) phenotypes and underwent epithelial to mesenchymal transition (EMT), and developed multidrug resistance. TR cells exhibited stronger drug efflux than parental NPC cells, leading to the reduction of intracellular drug concentrations and drug insensitivity. After screening the gene expression of ABC transporters and FOX molecules, we found that FOXM1 and ABCC5 were consistently overexpressed in the TR NPC cells and in patient tumor tissues. Further studies demonstrated that FOXM1 regulated abcc5 gene transcription by binding to the FHK consensus motifs at the promoter. The depletion of FOXM1 or ABCC5 with siRNA significantly blocked drug efflux and increased the intracellular concentrations of paclitaxel, thereby promoting paclitaxel-induced cell death. Siomycin A, a FOXM1 inhibitor, significantly enhanced in vitro cell killing by paclitaxel in drug-resistant NPC cells. This study is the first to identify the roles of FOXM1 in drug efflux and paclitaxel resistance by regulating the gene transcription of abcc5, one of the ABC transporters. Small molecular inhibitors of FOXM1 or ABCC5 have the potential to overcome paclitaxel chemoresistance in NPC patients.

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