Establishment of a mouse model bearing orthotopic temozolomide-resistant glioma].

Linyong Shi, Hong Li, Junwei Gu, Chong Song, Junjie Li, Lei Chen, Qiang Zhou, Songtao Qi, Yuntao Lu

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2021 Jan 30

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To establish a mouse model bearing orthotopic temozolomide (TMZ)-resistant glioma that mimics the development of drug resistance in gliomas in vivo. Seventy-eight adult C57BL/6 mice were randomly divided into 6 groups (n=13), including 3 TMZ induced groups with low, medium and high doses (5, 25, and 50 mg/kg, respectively) and 3 control groups. In each group, 5 mice were used for evaluating tumor size, 5 for observing survival, and 3 for collecting tumor tissues for primary cell culture. In low-dose TMZ induced group, 3 mice bearing orthotopic murine glioma GL261 cell xenografts received intraperitoneal injections of 5 mg/kg TMZ for 5 days followed by a 10-day washout period before collecting glioma tissues. Tumor cell suspensions were prepared and injected in the mice in the medium-dose group, which were treated with the same protocol but with an increased TMZ dose, and the tumor cells harvested from 3 mice were injected in the high-dose group. The mice bearing GL261 cell xenografts in the 3 control groups received no treatment or were injected with medium- or high-dose TMZ. Cell colony forming assay was used to assess TMZ resistance of each generation of the tumor cells; CCK8 assay was used to determine drug resistance index of the cells. The mouse models bearing TMZresistant glioma was successfully established. The cells from the high-dose induced group showed a significantly higher colony-forming rate than those from the high-dose control group (P < 0.05), and had a drug resistance 4.25 times higher than that of the cells from untreated control group. High-dose TMZ significantly reduced the tumor volume in the control group (P < 0.05) but not in the high-dose induced group (P < 0.01). The survival time of the tumor-bearing mice was significantly shortened in the high-dose induced group (P=0.0018). Progressive increase of TMZ doses in mice bearing orthotopic gliomas can effectively induce TMZ resistance of the gliomas.

Citation

Linyong Shi, Hong Li, Junwei Gu, Chong Song, Junjie Li, Lei Chen, Qiang Zhou, Songtao Qi, Yuntao Lu. Establishment of a mouse model bearing orthotopic temozolomide-resistant glioma]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 2021 Jan 30;41(1):69-74