Abstract
Glioma is the most difficult brain tumors to be cured in clinic. Despite receiving treatment, the survival days are still below two years. After performing the maximal surgical resection, the best strategy is always to combine with radiotherapy or chemotherapy, which depend on the malignancy and phenotype. The frequently used second-line of chemotherapeutic drug is cisplatin, widely used against carcinomas, germ cell tumors, lymphomas, and sarcomas. It has a simple mechanism dependent on interfering with DNA replication and inducing apoptosis. However, the drug resistance in tumor hypoxia, where the drug is difficult to reach, is one of problem need to be solved. In this study, we used a cisplatin analogue derived from the modification of cisplatin in order to target the hypoxia cells of a murine astrocytoma, ALTS1C1. According to the MTT assay, we found that the cytotoxicity of cisplatin and cisplatin analogue was slightly decreased under hypoxia. In animal studies, the administration of cisplatin changed the microvascular density and hypoxia percentage in early stage but cisplatin analogue didn’t. However, the administration of cisplatin analogue significantly increased the apoptotic cells in hypoxic area. In addition, this study also found that the combination of cisplatin with cisplatin analogue are more effective than single treatment to slow down the tumor growth, indicating that cisplatin analogue may have different working targets to its parental compound.