Loxiglumide (CR1505), a cholecystokinin antagonist, specifically inhibits the growth of human pancreatic cancer lines xenografted into nude mice

Abstract

Background. Cholecystokinin is thought to be an important factor regulating the growth of human pancreatic cancers. The study was designed to evaluate the effects of the cholecystokinin antagonist loxiglumide (CR1505) on the growth of human pancreatic cancer. Methods. Human gastrointestinal cancer xenografted tumors (one esophageal, one gastric, two colorectal, two biliary tract, and two pancreatic cancers) were transplanted into nude mice. The mice were given CR1505 at 250 mg/kg daily for 14 days, either subcutaneously or intragastrically, and the tumor volumes before and after treatment were compared. In vitro effects of CR1505 were assessed by measuring the DNA synthesis (3H‐thymidine incorporation). Results. CR1505 inhibited the growth of the two pancreatic cancer lines but did not inhibit the growth of the other lines. CR1505 also inhibited in vitro DNA synthesis in the two pancreatic cancer lines at lower concentrations than in the other lines. This pancreatic cancer‐specific inhibitory effect of CR1505 was retarded by exogenously administered cholecystokinin in one pancreatic cancer line but was augmented in the other line. The effect of CR1505 was inhibited by oral administration of the trypsin‐inhibitor camostate (FOY‐305) in both pancreatic cancer lines. Conclusions. These results suggest that CR1505 may specifically inhibit the growth of human pancreatic cancers and may be suitable for clinical study. However, its antiproliferative effect may not necessarily be dependent on its cholecystokinin‐antagonism but may be mediated through the proteolytic enzymes found in the lysosomes of the pancreatic cancer cells.

Expression of receptors for gut peptides in human pancreatic adenocarcinoma and tumour-free pancreas

“…However, stimulative, inhibitory or no effect of CCK on the growth of human pancreatic cancer cell lines or human pancreatic cancer xenografts in nude mice have been reported (Upp et al, 1987;Smith et al, 1990;Nio et al, 1993). Although the membrane fractions of some pancreatic cancer cell lines, such as MIA PaCa-2, BxPC-3, Capan-1, MDA-Amp-7 and MDA-Panc-28, expressed CCK-B receptors (Smith et al, 1994), no specific CCK binding was detected in the membranes of other pancreatic cancer cell lines (Singh et al, 1991).…”

Cardiovascular stents: overview, evolution, and next generation

“…On the other hand, VSMCs showed decreased proliferation and motility in comparison to the control (Hemshekhar et al 2016 ; Li et al 2015a ; Li et al 2015b ; Yang et al 2015 ). TiO 2 NTs, as an example, introduced an effective drug-free approach for vascular healing (Hemshekhar et al 2016 ; Nio et al 1993 ; Yang et al 2012 ).Nuhn et al ( 2017 ) provided both in vitro and in vivo data on the implantation of TiO 2 -NT-covered stents (Hemshekhar et al 2016 ; Li et al 2017 ; Li et al 2015a ). The in vivo results were in agreement with the in vitro study which showed reduced restenosis rates, promoted restoration of a functional endothelium when compared to the control.…”

Cholecystokinin receptor antagonist, loxiglumide, inhibits invasiveness of human pancreatic cancer cell lines

“…CCK receptors actiwtted by CCK may stimulate the growth of human pancreatic c; ncer cell lines [13]. LXG, a specific CCK receptor antagonst, has been reported to inhibit DNA synthesis and the gowth of human pancreatic cancer [16]. Many previous rep)rts have provided evidence in support of CCK receptors paying as growth factor receptors.…”

“…In Japan, a clinical trial has reported that LXG may be a useful agent for pmcreatitis [15]. A recent study has reported that LXG inh bits the growth of human pancreatic cancer cell lines [16]. tiowever, no known study has reported the relationship between CCK receptors and the invasiveness of human panc~eatic cancer cells.…”