Effective therapy of experimental human malignant melanomas with a targeted cytotoxic somatostatin analogue without induction of multi-drug resistance proteins

  • Authors:
    • Gunhild Keller
    • Andrew V. Schally
    • Attila Nagy
    • Benjamin Baker
    • Gabor Halmos
    • Jörg B. Engel
  • View Affiliations

  • Published online on: June 1, 2006     https://doi.org/10.3892/ijo.28.6.1507
  • Pages: 1507-1513
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Abstract

Malignant melanomas are characterized by a high intrinsic resistance to chemotherapy. Multiple drug resistance (MDR) can be mediated by transport proteins such as MDR-1, multidrug resistance-associated protein (MRP) or lung resistance protein (LRP). The cytotoxic analogue of somatostatin AN-238 consisting of 2-pyrrolinodoxorubicin (AN-201) linked to a somatostatin analogue RC-121 binds to receptors for somatostatin and is targeted to tumors expressing these receptors. We evaluated the expression of somatostatin receptors on human malignant melanoma tumor lines MRI-H255 and MRI-H187 and examined the effects of the targeted analogue AN-238 and its cytotoxic radical AN-201 on growth of these tumors in nude mice. We also studied the effects of AN-238 and AN-201 on the expression of MDR-1, MRP-1 and LRP by real-time PCR. AN-238 inhibited the growth of MRI-H255 and MRI-H187 tumors while AN-201 was ineffective. Blockade of somatostatin receptors by somatostatin analogue RC-121 abolished the effects of AN-238. Targeted therapy with AN-238 did not produce an induction of mRNA of MDR-1, MRP-1 or LRP. Our findings show that targeted chemotherapy with cytotoxic somatostatin analogue AN-238 inhibits the growth of malignant melanomas. AN-238 could provide a novel treatment approach for advanced malignant melanomas.

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June 2006
Volume 28 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Keller G, Schally AV, Nagy A, Baker B, Halmos G and Engel JB: Effective therapy of experimental human malignant melanomas with a targeted cytotoxic somatostatin analogue without induction of multi-drug resistance proteins. Int J Oncol 28: 1507-1513, 2006
APA
Keller, G., Schally, A.V., Nagy, A., Baker, B., Halmos, G., & Engel, J.B. (2006). Effective therapy of experimental human malignant melanomas with a targeted cytotoxic somatostatin analogue without induction of multi-drug resistance proteins. International Journal of Oncology, 28, 1507-1513. https://doi.org/10.3892/ijo.28.6.1507
MLA
Keller, G., Schally, A. V., Nagy, A., Baker, B., Halmos, G., Engel, J. B."Effective therapy of experimental human malignant melanomas with a targeted cytotoxic somatostatin analogue without induction of multi-drug resistance proteins". International Journal of Oncology 28.6 (2006): 1507-1513.
Chicago
Keller, G., Schally, A. V., Nagy, A., Baker, B., Halmos, G., Engel, J. B."Effective therapy of experimental human malignant melanomas with a targeted cytotoxic somatostatin analogue without induction of multi-drug resistance proteins". International Journal of Oncology 28, no. 6 (2006): 1507-1513. https://doi.org/10.3892/ijo.28.6.1507