Transcription Factors Sp1 And Sp3 Influence K562 Leukemia Cell Proliferation, Apoptosis And Drug Resistance

Objective: Acute leukemia (AL) is one of frequent malignant disease. Its incidence has an increasing tendency year by year. New chemotherapeutic agents and hemopoietic stem cell transplant have significantly enhanced the short and long term curative effects and prognosis, but some patients show primary or secondary multidrug resistance (MDR) which results in chemotherapy failure. MDR is one of the most important reasons for the failure of leukemia chemotherapy. MDR has a special broad-spectrum drug resistant phenomenon. Once cancer cells develop resistance to a certain anticancer drug, they will also resist many other drugs which even have unrelated structure and chemical mechanism.To establish a multidrug resistance cell line is essential for investigating the mechanism of MDR and finding out methods to reverse MDR. In previous studies, most of multidrug resistant cell lines were established by successive exposure to increasing dose of anti-tumor drugs, which is different from the common protocol of clinical chemotherapies using high dose drugs periodically. In this study, K562 leukemic cells were exposed to high dose of etoposide periodically. Therefore, the established MDR cell line was named K562/VP.Etoposide (VP-16) is one of the derivatives of podophyllotoxin and belongs to DNA topoisomerase II (Topo II) venenosus inhibitor. The major mechanism of VP-16 is to stabilize the cleavable complexes and to inhibit the rejoin of DNA, which led to DNA damage and cell death. VP-16 is probably one of the most useful drugs to treat AL. VP-16 combined with cytarabine (named protocol AE) had 45% efficacy rate, particular to M4 and M5. MDR is the major reason for chemotherapy failure of VP-16K562 cell line was established in 1977, whose genetic background was...