Reversal of drug resistance in breast carcinoma cells by anti-mdr1 ribozyme regulated by the tumor-specific MUC-1 promoter.
Multidrug resistance (MDR) is a serious obstacle for cancer chemotherapy. The aim of this study was to reverse MDR of breast carcinoma cells specifically by degrading mdr1 mRNA with anti-mdr1 ribozyme. Our strategy was to limit the expression of ribozyme to only breast-derived cells, but not other type of cells. The results showed the recombinant ribozyme pEGFP-RZmuc was expressed in two kinds of breast carcinoma cells, but not in non-breast-derived cancer cells. Evaluation of chemosensitivity showed that a 15-fold reduction in drug resistance for Adriamycin and a 32-fold reduction in drug resistance for Vinblastine were observed in the transfected cells. Our results demonstrate the efficacy and selectivity of pEGFP-RZmuc to reverse MDR in drug resistant breast carcinoma cells in vitro.
Gao
Peng
P
Department of Pathology, School of Medicine, Shandong University, Jinan 250012, China. gaopeng@sdu.edu.cn
Zhou
Geng-Yin
GY
Guo
Ling-Ling
LL
Zhang
Qing-Hui
QH
Zhen
Jun-Hui
JH
Fang
Ai-Ju
AJ
Lin
Xiao-Yan
XY
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation; D051549:Glutathione S-Transferase pi / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018396:Mucin-1 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016337:RNA, Catalytic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D018396:Mucin-1; D016337:RNA, Catalytic; D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D051549:Glutathione S-Transferase pi