Pkc Regulation Of The Expression Of The Multidrug Resistance Gene Mdr1 And Pkc Inhibitor On The Role Of Multidrug Resistance Reversal

Drug resistance is one of the most important factors leading to the high mortality of cancer in the world. In the light of American Association of Cancer Research(AACR), four hundred and ninety thousand people die of cancer each year. Among them, 61% of tumors are due to intrinsic drug resistance, including tumors from digestive system, respiratory system, urinary system, cerebral and central nerve system; 33% are due to acquired drug resistance, including tumors from head, neck, bone, connection tissue, skin, breast and endocrine as well as leukemia and lymphoma. That is to say, about 90% of death in tumor patients is associated with drug resistance. It is also found that tumor cells are not only resistant to chemotherapy, but also to radiotherapy. Over the past two decades understanding the mechanisms of drug resistance has become a central issue as its importance in medicine has assumed over-increasing significance. Although a number of different drug resistance mechanisms have been identified in the laboratory, perhaps the most intensively studied has been multidrug resistance(MDR). Classical MDR is defined as an acquired or intrinsic resistance to a broad array of structurally diverse natural products P-glycoprotein(P170, Pgp). MDR tumor cells typically have a reduced capacity to accumulated cytotoxic drugs that accounts at least in part for the resistance phenotype and appears to be a consequence of overexpression of the plasma membrane-spanning, energy-dependent drug efflux pump P-glycoprotein. Cultured cell lines with high Pgp expression have been shown to possess MDR gene amplification, and this is not consistent with that in the clinical setting. The resistant characteristics of...