MODULATION OF MULTIDRUG RESISTANCE BY VERAPAMIL OR MDR1 ANTISENSE OLIGODEOXYNUCLEOTIDE DOES NOT CHANGE THE HIGH SUSCEPTIBILITY TO LYMPHOKINE-ACTIVATED KILLERS IN MDR-RESISTANT HUMAN CARCINOMA (LOVO) LINE

Two sublines were derived from the colon adenocarcinoma line LoVo, the first one was sensitive (LoVo/H) and the second one was made resistant to doxorubicin (LoVo/Dx). 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− CD16+‐enriched lymphokine activated killers (LAK) or activated macrophages. In order to check whether this effect was due to different expression of glycoprotein PI70 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 LoVo/Dx with the calcium channel blocker verpamil (VRP), strongly impaired PI70 function as evaluated by reduced Dx resistance, without affecting the lysability of LoVo/Dx cells by LAKs. Moreover, the significant inhibition of PI70 expression resulting from the treatment of LoVo/Dx with mdrl antisense olideoxynucleotide also failed to change the high lysability of LoVo/Dx by LAKs. These results, therefore, indicate that molecules other than PI70 are involved in the increased lysis of LoVo/Dx subline by immune effectors and that downregulation of the PI70 expression or function will not reduce the potential effectiveness of cancer chemo‐immunotherapy. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company