摘要 |
The effects of suppressing c-<u>fos</u> oncogene expression on drug or radiation resistant mammalian cells are described. A2780S human ovarian carcinoma cells with resistance to actinomycin D were isolated and the resultant A2780AD cells exhibited the MDR phenotype. A hammerhead ribozyme designed to cleave <u>fos</u> RNA cloned into the pMAMneo plasmid was transfected into A2780AD cells. Induction of the ribozyme resulted in decreased expression of c-<u>fos</u>, followed by that of mdr-1, c-<u>jun</u>, and p53. Reversal of the MDR phenotype by the anti-mdr ribozyme occurred one-fourth as rapidly as that induced by the anti-<u>fos</u> ribozyme. These studies demonstrate the primacy of the c-<u>fos</u> oncogene in maintaining the resistant phenotype in human cancer cells. Thus, down regulation of <u>fos/jun</u> will make resistant cancer cells more sensitive to conventional treatment, i.e., cancer chemotherapeutic agents and/or radiation. |