Modulation of multidrug resistance by verapamil or mdr1 anti-sense oligodeoxynucleotide does not change the high susceptibility to lymphokine-activated killers in mdr-resistant human carcinoma (LoVo) line
✍ Scribed by Licia Rivoltini; Mario P. Colombo; Rosanna Supino; Dario Ballinari; Takashi Tsuruo; Giorgio Parmiani
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- French
- Weight
- 674 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Two sublines were derived from the colon adenocarcinoma line LoVo, the first one was sensitive (LoVolH) and the second one was made resistant to doxorubicin (LoVolDx). When tested for susceptibility to lysis by different types of immune effectors, LoVo/Dx appeared more sensitive than LoVo/H to the killing of CD3+CDS+CD16-, CD3-CD I6+-enriched lymphokine activated killers (LAK) or activated macrophages. In order to check whether this effect was due to different expression of glycoprotein P I70 between the two LoVo sublines (30% vs. 90% of positive cells), a pharmacological and genetic modulation of PI70 was carried out in LoVo cells. Treatment of LoVolDx with the calcium channel blocker verpamil (YRP), strongly impaired P I70 function as evaluated by reduced Dx resistance, without affecting the lysability of LoVo/Dx cells by LAKs. Moreover, the significant inhibition of P I70 expression resulting from the treatment of LoVolDx with mdrl antisense olideoxynucleotide also failed to change the high lysability of LoVolDx by LAKs. These results, therefore, indicate that molecules other than P I70 are involved in the increased lysis of LoVolDx subline by immune effectors and that downregulation of the PI70 expression or function will not reduce the potential effectiveness of cancer chemo-immunotherapy.