Loading...
Please wait, while we are loading the content...
Similar Documents
Spontaneous reversal of p-glycoprotein expression in multidrug resistant cell lines.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gréen, Henrik Lotfi, Kourosh Peterson, Curt |
| Copyright Year | 2003 |
| Abstract | Increased expression of P-glycoprotein encoded by the mdr-1 gene is a well-characterised mechanism for resistance to cancer chemotherapeutic drugs in cell lines. However, the P-glycoprotein expression after removal of the selection pressure has not fully been elucidated. The stability of P-glycoprotein expression in the presence (+) and absence (-) of vincristine (30 or 150 nM) was studied in multidrug resistant K562 cell lines (VCR30+, VCR150+, VCR30- and VCR150-) for 11 months. The P-glycoprotein protein and mdr-1 mRNA levels were determined at regular intervals using flow cytometry and real-time PCR, respectively. Chemosensitivity to a panel of antineoplastic drugs was measured using an MTT assay. The presence of vincristine (VCR30+ and VCR150+) resulted in high and stable levels of P-glycoprotein and mdr-1 mRNA during the whole period compared to wild type. As for the VCR30- and VCR150- subcultures, the expressions of P-glycoprotein and mdr-1 mRNA were stable for five months, and then the levels decreased rapidly. Concomitantly, the sensitivity to drugs known as P-glycoprotein substrates was restored. In conclusion, resistant cells growing in the presence of the inducing drug have a stable P-glycoprotein expression and resistance level, but removing the inducing drug may result in a sudden and rapid lowering of P-glycoprotein and mdr-1 mRNA levels as long as five months after drug withdrawal. |
| Starting Page | 297 |
| Ending Page | 304 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.diva-portal.org/smash/get/diva2:267309/FULLTEXT01.pdf |
| PubMed reference number | 14675464v1 |
| Volume Number | 93 |
| Issue Number | 6 |
| Journal | Pharmacology & toxicology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Antineoplastic Agents Cultured Cell Line Flow Cytometry K-562 P-Glycoprotein Substance Withdrawal Syndrome Vincristine Wild Type monooxyethylene trimethylolpropane tristearate |
| Content Type | Text |
| Resource Type | Article |
