Cisplatin treatment of C6 rat glioma in vivo did not influence copy number alterations and growth pattern of tumor-derived resistant cells

Abstract

To investigate whether the cisplatin treatment of C6 rat glioma in vivo impacts the copy number alterations (CNAs), proliferation and colony formation effi ciency (CFE) of tumor-derived cisplatin-resistant cells. Methods. The glioma modeling was performed by means of intracerebral stereotactic implantation of rat glioma C6 cells into the striatum region of rats. The rats received 20 % dimethyl sulfoxide DMSO (C6R1) or cisplatin (C6R4CIS and C6R5CIS) injected intraperitoneally (5 mg/kg) three times per week. After 10 injections, gliomas were resected and the cells were cultured for in vitro analysis. CNAs were analyzed by array comparative genome hybridization, proliferation by direct cell counting in hemocytometer, CFE by soft agar assay. Results. No signifi cant changes in the CNAs and CFE of cisplatin-treated rat glioma C6R4CIS and C6R5CIS cell lines were observed compared to the vehicle-treated control C6R1 cells. However, C6R5CIS but not C6R4CIS had a reduced proliferation. Interestingly, both cisplatin-and vehicle-treated brain-grown cells had a reduced proliferation and CFE in comparison to the parental C6 cells. Conclusions. Despite numerous reports on the destabilizing effects of cisplatin on genome and phenotype, the cisplatin treatment of C6 cells in vivo did not affect genome stability, CFE, and had an inconsistent effect on the proliferation in vitro. The rat brain microenvironment may potentially impact the growth characteristics of rat glioma cells.