Unexpected Growth-Promoting Effect of Oxaliplatin in Excision Repair Cross-Complementation Group 1 Transfected Human Colon Cancer Cells.

Abstract	The nucleotide excision repair protein excision repair cross-complementation group 1 (ERCC1) has been repeatedly shown to be involved in the sensitivity of cancer cells to platinum derivatives. In order to better understand this process, we transfected HCT-116 cells with a plasmid encoding ERCC1 and studied their in vitro and in vivo behaviour. No main differences were observed for sensitivity to platinum drugs, DNA repair capacity and clonogenicity in vitro. However, -ERCC1-transfected HCT-116 cells showed paradoxical behaviour in vivo with increased growth in mice treated with oxaliplatin as compared to untreated mice. The Trop2 protein was identified as being potentially involved in the underlying mechanism for these observations, as it was overexpressed in transfected cells. Our results suggest complex regulation of signalling in cancer cells exposed to cancer drugs.
Authors	Lars Petter Jordheim, Kamel Chettab, Emeline Cros-Perrial, Eva-Laure Matera, Charles Dumontet
Journal	Pharmacology (Pharmacology) Vol. 102 Issue 3-4 Pg. 161-168 ( 2018) ISSN: 1423-0313 [Electronic] Switzerland
PMID	30048976 (Publication Type: Journal Article)
Copyright	© 2018 S. Karger AG, Basel.
Chemical References	Antigens, Neoplasm Antineoplastic Agents Cell Adhesion Molecules DNA, Complementary DNA-Binding Proteins Organoplatinum Compounds TACSTD2 protein, human Oxaliplatin ERCC1 protein, human Endonucleases Cisplatin
Topics	Animals Antigens, Neoplasm (metabolism) Antineoplastic Agents (adverse effects, pharmacology) Cell Adhesion Molecules (metabolism) Cell Line, Tumor Cell Proliferation (drug effects) Cisplatin (pharmacology) Colorectal Neoplasms (drug therapy, enzymology, pathology) DNA Repair DNA, Complementary (administration & dosage, genetics) DNA-Binding Proteins (genetics, metabolism) Endonucleases (genetics, metabolism) Female Humans Mice Organoplatinum Compounds (adverse effects, pharmacology) Oxaliplatin Plasmids (administration & dosage, genetics) Transfection Xenograft Model Antitumor Assays

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