Synergistic activity of Hsp90 inhibitors and anticancer agents in pancreatic cancer cell cultures

Heat shock protein 90 (Hsp90) is a widely investigated target for anticancer therapy. The experimental Hsp90 inhibitors ICPD47 and ICPD62 demonstrated anticancer activity against colorectal, osteosarcoma and cervical cancer cell lines. However, their anticancer activity has not been investigated aga...

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Bibliographic Details
Published in:Scientific reports 2019-11, Vol.9 (1), p.16177-8, Article 16177
Main Authors: Daunys, Simonas, Matulis, Daumantas, Petrikaitė, Vilma
Format: Article
Language:English
Subjects:
13/106
14/63
5-Fluorouracil
631/80/304
692/4028/67/70
Antimetabolites
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antitumor activity
Antitumor agents
Bone cancer
Cell culture
Cell Line, Tumor
Cell viability
Cervical cancer
Cervix
Deoxycytidine - analogs & derivatives
Deoxycytidine - pharmacology
Doxorubicin
Doxorubicin - pharmacology
Fluorouracil - pharmacology
Gemcitabine
Heat shock proteins
HSP90 Heat-Shock Proteins - antagonists & inhibitors
HSP90 Heat-Shock Proteins - metabolism
Hsp90 protein
Humanities and Social Sciences
Humans
Hyperthermia
Investigations
multidisciplinary
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - metabolism
Osteosarcoma
Pancreatic cancer
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Sarcoma
Science
Science (multidisciplinary)
Spheroids
Synergistic effect
Tumor cell lines
Tumors
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Summary:Heat shock protein 90 (Hsp90) is a widely investigated target for anticancer therapy. The experimental Hsp90 inhibitors ICPD47 and ICPD62 demonstrated anticancer activity against colorectal, osteosarcoma and cervical cancer cell lines. However, their anticancer activity has not been investigated against pancreatic cancer cell lines yet, and there are no data about synergistic activity of these compounds in combination with clinically used anticancer agents. Pancreatic cancer cell lines, MIA PaCa-2 and PANC-1 were exposed to ICPD47 and ICPD62 alone and in combinations with antimetabolites gemcitabine (GEM), 5-fluorouracil (5-FU) and topoisomerase inhibitor doxorubicin (DOX). Effects on cell viability were determined by MTT assay. The synergistic activity was evaluated using Chou-Talalay method. Also, 3D cell cultures were formed using 3D Bioprinting method and the activity of each compound and their combinations was examined by measuring the size change of spheroids. The strongest synergistic activities were determined in combinations using all ratios of ICPD47 with GEM and ICPD62 with GEM in MIA PaCa-2 cell line (combination index
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-52652-1