Chemosensitisation by verapamil and cyclosporin a in mouse tumour cells expressing different levels of p-glycoprotein and cp22 (sorcin)

ABSTRACT The relationships between resistance to adriamycin, vincristine, colchicine and etopside, expression of P-glycoprotein and CP22 (sorcin), and resistance modification by verapamil

and cyclosporin A have been studied in a panel of multidrug-resistant (MDR) mouse tumour cell lines. Whereas there was a generally good correlation between the degree of resistance and the

amount of P-glycoprotein, no relationship between resistance and CP22 expression was seen. At 3.3 microM verapamil, the sensitisation of the MDR cell lines was no greater than that of the

parent line. At 6.6 microM verapamil, however, sensitisation of the MDR lines generally exceeded that of the parent line, although the line CR 2.0, expressing very high levels of

P-glycoprotein was an exception. Little sensitisation to etoposide was seen in any of the lines. When cyclosporin A was used as the sensitiser at either 2.1 or 4.2 microM, there was a

greater effect in lines expressing moderate to high levels of P-glycoprotein than in the parent line, although this tendency was less for adriamycin than for the other cytotoxics.

Sensitisation to etoposide was much greater with cyclosporin A than with verapamil. At low levels (less than 1 microM) of CsA, however, sensitisation to colchicine was greater in the parent

line than in cell line CR 2.0. These studies indicate that chemosensitisation by verapamil and cyclosporin A is extremely complex, depending upon sensitiser dose, the particular cytotoxic

and the cell line. At low doses of the sensitisers, the sensitisation may be greater in lines expressing low levels of P-glycoprotein than in lines showing high levels. Access through your

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Open access 06 August 2024 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * MRC Clinical Oncology, MRC Centre, Cambridge, UK PR Twentyman Authors * PR Twentyman View author publications You can

also search for this author inPubMed Google Scholar * JG Reeve View author publications You can also search for this author inPubMed Google Scholar * G Koch View author publications You can

also search for this author inPubMed Google Scholar * KA Wright View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Twentyman, P., Reeve, J., Koch, G. _et al._ Chemosensitisation by verapamil and cyclosporin A in mouse tumour cells expressing different

levels of P-glycoprotein and CP22 (sorcin). _Br J Cancer_ 62, 89–95 (1990). https://doi.org/10.1038/bjc.1990.235 Download citation * Issue Date: 01 July 1990 * DOI:

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