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For the treatment of colorectal cancer many new products are on the market, but often with drug resistance and side effects. Looking for new pharmacological agents with improved properties, a new substance (BTB 14431) was discovered by using the kinase inhibitor emodin and “in silico screening”. It was already examined once in vivo in a tumor suspension model in a previous experiment. Various studies have shown that emodin induces apoptosis, inhibits cell proliferation and suppresses angiogenesis and so may reduce tumor growth. In this experimental study the effect of emodin and BTB 14431 on the growth of advanced tumors with relation to differences in the mode of application and the dosage has now been investigated. A standardized animal model of cancer has been established and the release of vital tumor cells by an oncotic intervention was simulated. For this purpose 100 rats (WAG-RIJ) received a sterile intraperitoneal injection of 105 syngenetic colon adenocarcinoma cells (CC-531) by laparotomy. In addition, the animals were given a subcutaneous injection of also 105 syngenetic tumor cells of the same cell type, which should simulate peripheral metastases. To investigate the systemic influence of the newly identified substance BTB 14431 and of emodin to solid tumors half of the animals were treated by ports in the external jugular vein over a week in a 12-hour rhythm 28 days after cellapplication (control group: treatment with Ringer’s solution, treatment groups: treatment with 0,3 mg/kg bw BTB 14431, 1,7 mg/kg bw BTB 14431, emodin 2,5 mg/kg bw or emodin 5 mg/kg bw).
The other half of the animals received intraperitoneal injections of the intermittent therapy. Three weeks after treatment, the animals were euthanized and the tumor weights were determined. As a result of this experiment, a dose-dependent effect of emodin and BTB 14431 on the growth of tumors could be shown. Moreover, emodin seems to be more potent and better tolerated than BTB 14431. However, this is dependent on both the dose and the mode of application. The best results were shown in the groups with intravenous emodin treatment in one of the dosages or BTB 14431 0,3 mg/kg.
The animals in this group increased more in weight and the tumors had a lower weight than in the control group. Furthermore, a better efficacy of treatment for intravenous application was observed in the mentioned groups as compared to the intraperitoneal application. In the groups with animals treated intraperitoneally there was only a difference in the weight of the tumor mass compared to the control group treated with 5 mg/kg KG emodin. BTB 14431 did not show the expected effect at higher doses.