Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses multidrug resistance (MDR) and induces apoptosis in MDR gastric carcinoma cells. In our previous study, cisplatin proved to be a sensitizing agent for TRAIL. To study the synergistic effects of cisplatin and TRAIL, we investigated the mechanism by which TRAIL reverses multidrug resistance, the role of c-myc in modulating the death receptors DR4 and DR5 and the relationship between cisplatin and cytochrome c (cyt c) release in SGC7901/VCR and SGC7901/DDP cells. We found that after treatment with TRAIL, the DNA-PKcs/Akt/GSK-3β pathway, which is positively correlated with the levels of MDR1 and MRP1, was significantly inhibited and that this tendency can be abolished by Z-DEVD-FMK (a specific caspase 3 inhibitor). We also found that suppression of c-myc by siRNA reduced the expression of DR4 and DR5 and that transfection with a pAVV-c-myc expression vector increased the expression of DR4 and DR5. Moreover, cisplatin increased the expression of c-myc in the presence of TRAIL, and there is a clear increase in cyt c release from mitochondria with the increasing concentrations of cisplatin. Meanwhile, the intrinsic death receptor pathway of caspase 9, as well as the common intrinsic and extrinsic downstream target, caspase 3, was potently activated by the release of cyt c. Together, we conclude that in TRAIL-treated MDR gastric carcinoma cells, cisplatin induces the death receptors DR4 and DR5 through the up-regulation of c-myc and strengthens the activation of caspases via promoting the release of cyt c. These effects would then be responsible for the TRAIL sensitization effect of cisplatin.

The spectrum of normalized Laplacian matrix of a network has attracted more and more attention because it is related to the structural properties and dynamical aspects of the network, specially in random walks. In this paper, we study the spectra and their applications of normalized Laplacian matrices for weighted level-3 Sierpiński graphs that are constructed in an iterative way. We analytically obtain all the spectra from two successive generations by applying the decimation method. Using the obtained spectra, we then derive closed-form expressions for their eigentime identity and number of spanning trees.

Much information on the structural properties and some relevant dynamical aspects of a graph can be provided by its normalized Laplacian spectrum, especially for those related to random walks. In this paper, we aim to present a study on the normalized Laplacian spectra and their applications of weighted level-[Formula: see text] Sierpiński graphs. By using the spectral decimation technique and a theoretical matrix analysis that is supported by symbolic and numerical computations, we obtain a relationship between the normalized Laplacian spectra for two successive generations. Applying the obtained recursive relation, we then derive closed-form expressions of Kemeny’s constant and the number of spanning trees for the weighted level-[Formula: see text] Sierpiński graph.