Effect of short-term morphine exposure on P-glycoprotein expression and activity in cancer cell lines.
Multidrug resistance (MDR) is a common problem in various types of cancer. One important factor in the development of MDR is overexpression of P-glycoprotein, encoded by the MDR1 gene. Morphine is the opioid of choice for moderate to severe cancer pain, and is a substrate of P-glycoprotein. Recently, morphine has been shown to induce P-glycoprotein expression in the rat brain. Using Western blot analysis and cytotoxicity assays respectively, we have investigated the effects of short-term (72 h) morphine treatment on P-glycoprotein expression in a panel of human cancer cell lines, and its effects on cellular resistance to the known P-glycoprotein substrates, vinblastine and colchicine. The effect of morphine on P-glycoprotein expression and activity in the mouse fibroblast NIH-3T3 cell was assessed to establish whether morphine effects are species specific. Short-term exposure to morphine did not result in any significant differences in P-glycoprotein expression or activity in any cancer cell lines. Morphine pre-treatment resulted in a moderate but significant increase in sensitivity of NIH-3T3 cells to vinblastine, but not colchicine. This study suggests that morphine effects may be cell-type specific. Importantly, however, it appears that short-term morphine treatment does not affect the MDR phenotype of tumour cells.
Pajic
Marina
M
Children's Cancer Institute of Australia for Medical Research, Randwick, Sydney, NSW 2031, Australia. mpajic@ccia.org.au
Bebawy
Mary
M
Hoskins
Janelle M
JM
Roufogalis
Basil D
BD
Rivory
Laurent P
LP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D014747:Vinblastine / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014747:Vinblastine; D009020:Morphine; D003078:Colchicine