Proteomic Analysis Of Mechanism Of Multidrug Resistance In Human Gastric Cancer

Multidrug resistance (MDR) describes a phenomenon of cross-resistance of tumor cells to several structurally unrelated chemotherapeutic agents after exposure to a single cytotoxic drug. Resistance to anticancer drugs is a major obstacle preventing the effective treatment of tumors. Recent years several mechanisms have been found to contribute to MDR, involving proteins such as P-gp (P-glycoprotein), MRP (multidrug resistance related protein), LRP (lung resistance related protein), BCRP (breast cancer multidrug resistance related protein), TOP II (topoisomerase II) and GST (glutathione-S-transferase), etc. The phenomenon of MDR is also known to be a multifactorial event in which several mechanisms act simultaneously. On the one hand, tumor cells could greatly decrease the intracellular concentration of cytotoxic drugs by the ATP driven efflux pump functions of P-gp, MRP and BCRP. On the other hand, anticancer drugs could not arrive at their targets because of transportation of the intracellular cytotoxic drugs to other subcellular structures by LRP. Finally, structural alterations in the drug target enzymes and proteins increased their detoxification, and alterations in cellular metabolism enhanced the ability of tumor cells to repair DNA damage and resistant to apoptosis. Although these pathogenesis studies on MDR of tumors have been undertaken successfully, the mechanisms of MDR are intricate and have not been fully elucidated yet.Gastric cancer is one of the most common malignant tumors with a very high mortality worldwide. There are marked geographic variations in gastric cancer incidence, with the highest rates in China, Korea, Japan and South America, and much lower rates in Western Countries. Contemporary chemotherapies for gastric cancer, usually containing 5-fluorouracil (5-FU) and/or cisplatin, demonstrate response rates in the 20～40% range, with median survival between 6 and 12 months. The MDR mechanisms in gastric cancer cells have been broadly explored, but they are still unclear. Vincristine-resistant SGC7901/VCR, which derived from human gastric cancer cell line SGC7901 by stepwise selection in...