The samples for each PCR were prepared in triplicate. The GAPDH gene was used as the control. Data sets were analyzed and amplification plots were obtained automatically selleck bio by the 7500 Fast System Software. The comparative threshold cycle method, which converts dif ferences of cycle numbers to the ratio of the test gene/ control gene, was used to normalize the gene expression levels to GAPDH mRNA. PPI network and signaling pathway analysis Proteins were analyzed for their interactions and signaling pathways using Search Tool for the Retrieval of Interacting Genes/Proteins database version 9. 0 and the Ingenuity Pathways Analysis software, respectively. Introduction The efficacy of chemotherapy is strongly dependent on the transport of anticancer drugs to tumour cells and their responses to the administrated drug .

both can be compromised significantly by complexities associated with cancer, which is a disease of collective dysregulations across multiple scales. To exert therapeutic effects, anticancer drugs must reach tumour cells with a sufficiently high concentration. Limited penetration is one of the major causes of failure of chemotherapy treatment of solid tumours. The first obstacle to most blood borne chemotherapeutic agents is posed by the abnormal and chaotic tumour vasculature, which limits tumour blood flow and consequently the sup ply of drugs and nutrients. After crossing Anacetrapib the capillary wall, anticancer drugs must penetrate through the tumour interstitium, where drug distribution is determined by the effectiveness of drug transport by diffusion and convection as well as drug consumption.

Elevated interstitial fluid pressure in solid tumours hinders convective transport, rendering diffusion the dominant mechanism for interstitial drug transport. Drug diffusivity depends strongly on the physicochemical properties of the specific drug, selleck chem such as molecular weight, shape, charge and solubility. Drug consumption involves drug binding, sequestration and metabolism, which can be altered by microenvironmental conditions, such as extracellular matrix composition and structure, cell packing density and the presence of tumour acidity. For most anticancer drugs, it is necessary for drug mole cules to transport across cell membranes to reach the target molecules and interact with them, as a consequence, triggering cellular signal transduction. Cellular signalling is one of the important characteristics of every living cell in that it governs the basic cellular activities by perceiving and correctly responding to external/internal stimuli. Anticancer drugs as stress stimuli can regulate/trigger cell signalling to kill cells or affect their cellular responses, which might be directly associated with fatal consequences of cancer.