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001-es BibID:	BIBFORM075362
Első szerző:	Oláh Gábor (gyógyszerész)
Cím:	Experimental therapy of doxorubicin resistant human uveal melanoma with targeted cytotoxic luteinizing hormone-releasing hormone analog (AN-152) / Gábor Oláh, Nikoletta Dobos, György Vámosi, Zsuzsanna Szabó, Éva Sipos, Klára Fodor, Kristóf Harda, Andrew V. Schally, Gábor Halmos
Dátum:	2018
ISSN:	0928-0987
Megjegyzések:	Background: Cytotoxic analogs of LHRH (luteinizing hormone-releasing hormone) can be successfully used for the treatment of hormone-dependent cancers such as prostatic, ovarian, endometrial, but our knowledge about their e?ect on hormone-independent cancers such as human uveal melanoma (UM) is limited. Previously, we have demonstrated that 46% of UM express full-length LHRH receptors. This ?nding has led us to further examine the mechanism of action of LHRH receptor based targeted therapies in this malignancy. Aims: In the present study we investigated the cellular uptake of doxorubicin (DOX) and cytotoxic LHRH analog AN-152 (AEZS-108, zoptarelin doxorubicin) on human UM cell lines (OCM3) and its DOX resistant form OCM3 by confocal laser scanning microscopy. The LHRH receptor expression was characterized by RTPCR and immunocytochemistry. Results: We were able to establish a new, stable and DOX resistant human UM cell line OCM3 DOX320 . Our results demonstrated the expression of splice variants and isoforms of receptor for LHRH in OCM3 UM cell line and its doxorubicin resistant form OCM3 . It has been revealed by MTT assay that AN-152 inhibited cell proliferation in a dose dependent manner in OCM3 DOX320 DOX320 cells. Furthermore, receptor-mediated uptake of AN-152 was demonstrated using confocal laser scanning microscopy in both cell line. Conclusions: Our results suggest that the antiproliferative e?ect of AN-152 can be detected even if only LHRH receptor isoforms are expressed. Our study also demonstrates the LHRH receptor-mediated uptake of AN-152 in DOX resistant OCM3 DOX320 cells Our experiments provide new insights into a potential targeted therapy of UM and give further details about the accumulation of AN-152 in hormone-independent DOX-resistant cells expressing splice variants of the LHRH receptors.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Targeted cancer therapy Luteinizing hormone-releasing hormone (LHRH) Doxorubicin resistant cancer Human uveal melanoma Targeted cytotoxic LHRH analog AN-152 (AEZS-108, zoptarelin doxorubicin)
Megjelenés:	European Journal Of Pharmaceutical Sciences. - 123 (2018), p. 371-376. -
További szerzők:	Dobos Nikoletta (1981-) (biológus) Vámosi György (1967-) (biofizikus) Szabó Zsuzsanna (1973-) (biológus, biológia-kémia szakos középiskolai tanár) Sipos Éva (1989-) (gyógyszerész) Molnár-Fodor Klára (1989-) (biotechnológus) Harda Kristóf Máté (1989-) (gyógyszerész) Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Pályázati támogatás:	K 81596 OTKA TÁMOP-4.2.2.A-11/1/KONV-2012-0025 TÁMOP TÁMOP-4.2.2/B-10/1-2010-0024 TÁMOP EFOP-3.6.1-16-2016-00022 EFOP GINOP-2.3.2-15-2016-00043 GINOP
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