ABSTRACT
Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness. The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity. Among them, thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection. This smart biomaterial could transform to semisolid phase when the temperature increased. Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe, efficient, and sustained inner ear drug administration. This article introduces the key techniques and the latest progress in this field.
ABSTRACT
The Wingless-type protein 7a (Wnt7a) plays an antiproliferative role in non-small-cell lung cancer (NSCLC). Previous studies have indicated that Wnt7a expression was downregulated in radiation-resistant NSCLC cells. However, little is known about its biological functions and molecular mechanisms in radiosensitivity of NSCLC. Thus, NSCLC cell proliferation and apoptosis in response to Wnt7a overexpression and/or radiation were determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assay and flow cytometry, respectively. The activation of the Wnt/cJun N-terminal kinase (JNK) and Wnt/ß-catenin signaling pathways were further examined by western blot in NSCLC cell lines H1650 and A549. Wnt7a overexpression combined with radiation-inhibited cell proliferation and induced apoptosis in NSCLC cell lines compared to Wnt7a overexpression or radiotherapy alone. In addition, the phosphorylation of JNK, but not ß-catenin, was congruent with the changes in Wnt7a overexpression and/or radiation. Moreover, the Wnt/JNK pathway could induce the apoptosis of NSCLC cells through the mitochondrial pathway. Inhibition of the Wnt/JNK signaling pathway by SP600125, a JNK inhibitor, contributed to proliferation induction in NSCLC cells. Taken together, these results showed that Wnt7a overexpression sensitized NSCLC cell lines to radiotherapy through the Wnt/JNK signaling pathway.
