Enhancement of cisplatin efficacy by thalidomide in a 9L rat gliosarcoma model

Abstract

With the aim of improving the treatment of glioblastoma multiforme, we investigated the potential of thalidomide to enhance the effectiveness of cisplatin chemotherapy in a rat glioma model. Female F344 rats were implanted with 9L gliosarcoma tumors either intracranially or subcutaneously and treated with 1 mg/kg cisplatin injected i.p. or with 1% thalidomide in the food or with these treatments combined. Cisplatin in combination with thalidomide significantly reduced both the subcutaneous tumor volume at 30 days to 22 +/- 5% (mean +/- SEM, P < 0.001) and the intracranial tumor volume at 18 days to 44 +/- 15% (P < 0.05) of that with cisplatin alone. Thalidomide selectively increased the cisplatin concentration 10-fold in intracranial tumors (P < 0.05) and 2-fold in the subcutaneous tumors (P < 0.05) without increasing its concentration in major organs including brain and kidney. Cisplatin combined with thalidomide caused a significant decrease in vascular endothelial growth factor (VEGF) levels by 73% in intracranial tumors (P < 0.05) and by 50% in subcutaneous tumors (P < 0.05) and caused the level of active hepatic growth factor (a-HGF) to double in both the subcutaneous and intracranial tumors (P < 0.05), suggesting this treatment altered the vasculature in these tumors. We conclude the increased efficacy of cisplatin in the presence of thalidomide was due to the selective increase in cisplatin concentration within the tumors and speculate that this is the result of thalidomide or the cisplatin/thalidomide combination, selectively altering the tumor vasculature. Based on the selective effects of thalidomide on tumor cisplatin concentrations and the resulting increase in efficacy, thalidomide may also increase the efficacy of other drugs that are presently considered ineffective against glioma.

Honokiol Crosses BBB and BCSFB, and Inhibits Brain Tumor Growth in Rat 9L Intracerebral Gliosarcoma Model and Human U251 Xenograft Glioma Model

“…Meanwhile, the results suggested that honokiol might possess a potential therapeutically strategy against liver cancer and lung cancer except brain cancer. In addition, in previous study the distribution of cisplatin, as one of malignant gliomas treatment drugs, showed that cisplatin accumulated mainly in kidney, liver, lung and heart [29]. From the above results, we could gain a conclusion that the two drugs, whether honokiol or cisplatin, mainly accumulated in lung, liver and kidney.…”

In Vivo Evaluation of Paclitaxel-Loaded Lipid Nanocapsules After Intravenous and Oral Administration on Resistant Tumor

“…In our case, the activity of the different formulations of Ptx was evaluated on a syngeneic model: a subcutaneous isograft of 9L tumor cell performed in Fisher rats. This model has been used before in the same conditions by other teams [52,53]. The use of a syngeneic model was justified by the fact that with this kind of model the immune system of the animal remains active which is very important to evaluate nanomedicine that can be rapidly inactivated by the immune system [36].…”

Streptavidin: A Novel Immunostimulant for the Selection and Delivery of Autologous and Syngeneic Tumor Vaccines

“…Buprenorphine (Temgesic, 0.4 mg/kg; Schering-Plough) was administered subcutaneously for pain relief. Following recovery, rats were monitored daily for signs of distress as described previously (11).…”