Reversal of drug resistance in multidrug-resistant human lung cancer cells by retrovirus-mediated MDR1 antisense RNA

摘要

Human lung cancer is one of the commonest cancers in the world, and its incidence and mortality are very high. About 50% of the patients with lung cancer can be treated with surgery, and another 50% need chemotherapy because of cancer metastasis. Additionally the patients already having surgical treatment often need chemotherapy. However, the chemotherapy often loses its function on these patients, especially in non-small-cell lung cancer (NSCLG). Many studies have shown that one of the important causes of chemotherapeutic failure is that tumor produces drug resistance caused by overexpression of multidrug resistance gene (MDR1) and its product p-glycoprotein (Pgp). To make good chemotherapeutic protocols, MDR1 gene should be detected before chemotherapy. So the drug-resistant problem is the key in malignant tumor treatment. Antisense is a new method inhibiting gene expression and playing important roles, and is used widely in antivirus and antitumor as well as gene therapy. GAOK cell line was a multidrug-resistant strain selected with doxorubicin from human lung adenocarcinoma, which overexpressed MDR1 gene. To reverse the GAOK's drug resistance, we transferred MDR1 antisense RNA into the cells by retrovirus and studied its function, and tried to explore the possibility of reversal of tumor drug resistance.