Mechanism On The Regulation Of Multi-drug Resistance Of Cancer By Multifunctional Carbon Nanoshpere

Human breast cancer (MCF-7) is the biggest threat for women, due to the chronictreatment with chemotherapic drug, which could cause resistant to similar drugs, andfinally result in Multidrug Resistance (MDR). Even though by increasing drug dose, itstill useless, meanwhile, drug itself has some toxicity, which could also do hame topatient, increase the economic burden and waste resources. Because of the variety typesof drug resistance, complexity of molecule mechanism, it is very urgent to explore thenew treatment and possible mechanism, and guide the clinical MDR treatment.This thesis aims to research on the regulating of MCF-7/ADR by nanotechnology,which could realize both hyperthermia and chemotherapy by means of DOX loadedHollow Carbon Nanosphere (HCNs), and then focuse on its molecule mechanism.Whenirradiate with fs laser, HCNs@DOX could realize temperature rise, the heat couldinduce MCF-7/ADR become more sensitivity to DOX, and also could cause DOXrelease and target to nucleus and lead to cell death. Therefore, a mild laser powerdensity can modulate the drug-resistance related genes. This photothermal effecttriggers higher expression of heat shock factor (HSF-1) trimers and depresses theexpression of P-glycoprotein (P-gp) and mutant p53. In turn, both drug accumulation inthe MCF-7/ADR and their sensitiveness to drugs can be greatly enhanced.Finally, we conclude that:1) HCNs@DOX could obviously increase the amountof DOX in the MCF-7/ADR, and the drug release efficiency is related to pH andtemperature,2) DOX could reach to the nucleus after NIR treatment and could causethe change of function and structure of MCF-7/ADR, the elevated ROS level play akey role in the cell sensitiveness, such as cell uptake of DOX and cell vitality,3) NIRhas different effectiveness with water bath on the regulation of MDR, which reflect theinner-outer heat difference;4) The possible mechanism is HSF-1mediated p53andmdr-1regulation, and another mechanism may be the change of lysosomepermeability mediated mitochondrial damage，and cause the elevation of ROS level,which could futher regulate the MDR related signal pathway.