title: Marginal effects of glucose, insulin and insulin-like growth factor on chemotherapy response in endothelial and colorectal cancer cells.
abstract: Resistance to chemotherapy is a major clinical issue for patients with colorectal cancer. Obesity has been associated with a poorer outcome and is a possible mechanism of resistance. The aim of the present study was to investigate the effect of obesity-related factors on the cell response to standard chemotherapy in stromal and colorectal cancer cells. Viability was measured following the treatment of colorectal cancer cell lines (WiDr and SW620) and stromal cells (human microvascular endothelial cells)in vitrowith 5-fluorouracil, irinotecan and oxaliplatin under obesity-related conditions [elevated levels of insulin, insulin-like growth factor-1 (IGF-1) and glucose] and compared with non-elevated conditions. Obesity-related conditions alone increased cell viability and in selected cases, accumulation of the transcription factor, hypoxia-inducible factor-1. However, these conditions did not consistently increase resistance to the chemotherapy agents tested. The combination of IGF-1 and extremely low-dose chemotherapy significantly induced cell viability in WiDr colorectal cancer cells. Thesein vitroresults may have clinical importance in an environment of increasing rates of obesity and colorectal cancer, and the frequent under-dosing of obese cancer patients.
authors.affiliation: Mackenzie Cancer Research Group, Department of Pathology, University of Otago Christchurch, Christchurch 8140, New Zealand.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Volkova
authors.affiliation: Mackenzie Cancer Research Group, Department of Pathology, University of Otago Christchurch, Christchurch 8140, New Zealand ; Canterbury Regional Cancer and Blood Service, Canterbury District Health Board, Christchurch 8140, New Zealand.
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Robinson
authors.affiliation: Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch 8140, New Zealand.
authors.forename: Jinny
authors.initials: J
authors.lastname: Willis
authors.affiliation: Mackenzie Cancer Research Group, Department of Pathology, University of Otago Christchurch, Christchurch 8140, New Zealand.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Currie
authors.affiliation: Mackenzie Cancer Research Group, Department of Pathology, University of Otago Christchurch, Christchurch 8140, New Zealand.
authors.forename: Gabi U
authors.initials: GU
authors.lastname: Dachs
keywords: fluorouracil; irinotecan; low dose; oxaliplatin; proliferation; stroma