Drug-resistant lung tumor cells usually refers to tumor cells sensitivity to anticancer drugs decreased or disappeared. Multidrug resistance (MDR) refers to a number of tumor cells has not been in contact, structure and mechanism of the drugs are not the same cross-resistance phenomenon. Have found that lung tumor cells resistant to cell membrane glycoprotein levels and resistance and reduced intracellular drug accumulation was positively correlated. Therefore, such a membrane glycoprotein known as the p-glycoprotein, the gene encoding this protein is known as MDR genes.
MDR drug resistance of tumor cells in clinical phenotype, there are two situations: one is a congenital MDR, which has some tumors without chemotherapy for MDR phenotype, characterized by normal tissue there is the original p-glycoprotein expression of such as junction cancer , meningioma, etc.; the other is acquired MDR, that after a period of chemotherapy did not emerge until after the MDR, such as leukemia, ovarian cancer and so on.
Produced by mechanism of MDR can be summarized into four aspects: in the cell membrane to reduce the level of drug uptake and efflux increased, the absolute intracellular concentration of drug decreased; organelles in the cytoplasm and subcellular distribution of the drug level changes to the the role of drugs can not close its target, causing reduced effective concentration of drug; cellular detoxification system and enhance the roles of DNA repair systems, so that drugs to be inactivated and the cancer drug-induced DNA damage repair in a timely fashion; drug targets in terms of quality and quantity changes, mainly referring to decreased expression of topoisomerase E, and the point mutation, decreased activity, decreased this enzyme as a target of drug toxicity.
Use of ribozymes and antisense nucleotides can be reduced in the mRNA level of expression of P-glycoprotein and reverse MDR. However, widely used in clinical MDR reversal agents, or are chemosensitizer, in addition to research more calcium antagonists, the recently discovered p-glycoprotein monoclonal antibody and surrounded by amphotericin A and its derivatives combined with a synergistic effect. Glue broken four P-glycoprotein with mortar not only an effective regulator, but also non-reversible mechanism of p-glycoprotein MDR.
Clinical application chemosensitizer required attention to the following problems: Patients must be monitored continuously using the MDR phenotype changes; to consider not only the toxicity of sensitizer itself, but also consider increasing the toxicity of chemotherapy drugs, as p-glycoprotein is inhibited will be protected by the organizations (such as the brain) increase in the drug; in vitro results for the body to move carefully, the body is far more complex when the cell culture in vitro.
Lung tumor cells resistant to clinical treatment, if the following measures may delay the occurrence of MDR: early adopters of high-dose chemotherapy combined with chemotherapy; short-term focus on chemotherapy; patients before treatment of tumor sensitivity test, select the composition of the tumor sensitive drugs chemotherapy; pharmacokinetics during chemotherapy, measured, and adjust the treatment plan to achieve individual treatment; bone marrow transplantation.