Biopolym. Cell. 2015; 31(3):209-217.
Cisplatin treatment of C6 rat glioma in vivo did not influence copy number alterations and growth pattern of tumor-derived resistant cells
1Stepanenko A. A., 2, 3Baklaushev V. P., 4Vassetzky Y. S., 1Dmitrenko V. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Pirogov Russian National Research Medical University
    1, Ostrovitianov Str., Moscow, Russian Federation, 117997
  3. Federal Research and Clinical Centre, Federal Medical-Biological Agency
    28, Orekhovy Blvd, Moscow, Russian Federation, 115682
  4. CNRS UMR 8126, Universit Paris-Sud 11, Institut Gustave Roussy
    114, rue Edouard Vaillant, Villejuif, France, 94805


Aim. To investigate whether the cisplatin treatment of C6 rat glioma in vivo impacts the copy number alterations (CNAs), proliferation and colony formation efficiency (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 significant 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.
Keywords: aneuploidy, chromosome instability, drug resistance, tumor evolution, heterogeneity.


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