Wild-type p53 gene increases MDR1 gene expression but decreases drug resistance in an MDR cell line KBV200.
Inactivation of p53 gene and overexpression of MDR1 gene are both associated with drug resistance. Previous studies have suggested that p53 gene can modulate the expression activity of MDR1 gene promoter in a promoter-CAT system. In the present study, wild-type p53 gene cDNA was introduced into a multidrug-resistant cell line, KBv200, in which endogenous p53 gene is aberrant. In wt-p53 transfected cells, the expression of MDRI gene was significantly increased, accumulation of adriamycin (ADM) was decreased, and the sensitivity to vincristine (VCR), ADM and 5-fluorouracil (5-FU) was increased compared with the parent KBv200 cells. After treatment with ADM and VCR, the p53-transfectants were more susceptible to apoptosis. The results suggest that the increase in drug sensitivity of the cells may be, at least in part, due to p53-dependent apoptosis induced by anticancer agents.
Li
Z H
ZH
Department of Biochemistry, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
Zhu
Y J
YJ
Lit
X T
XT
D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics* / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007624:KB Cells / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
D006023:Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger