Effects of an irinotecan derivative, ZBH‑1208, on the immune system in a mouse model of brain tumor and its antitumor mechanism

Hui,Yuzuo; Gao,Zhiyu; Ren,Songtao; Wang,Yunhua; Ma,Xiaoping

doi:10.3892/mmr.2017.7370

Effects of an irinotecan derivative, ZBH‑1208, on the immune system in a mouse model of brain tumor and its antitumor mechanism

Authors:
- Yuzuo Hui
- Zhiyu Gao
- Songtao Ren
- Yunhua Wang
- Xiaoping Ma
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Affiliations: Department of Neurosurgery, Liaocheng People's Hospital and Clinical Teaching Hospital, Taishan Medical College, Liaocheng, Shandong 252000, P.R. China, Department of Gynecology and Obstetrics, Liaocheng People's Hospital and Clinical Teaching Hospital, Taishan Medical College, Liaocheng, Shandong 252000, P.R. China
Published online on: August 28, 2017 https://doi.org/10.3892/mmr.2017.7370
Pages: 6340-6345

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Abstract

The present study aimed to evaluate the inhibitory effects of an irinotecan derivative, ZBH‑1208, on brain tumors, and to explore the underlying molecular mechanisms. To determine the effects of ZBH‑1208, a brain tumor mouse model was established by transplanting B22 cells. Subsequently, the visceral indices of immune organs and white blood cell counts were determined, and the effects of ZBH‑1208 on the expression levels of cell cycle‑related proteins were assessed by western blotting. The tumor inhibition rates of 20 and 40 mg/kg ZBH‑1208 were 11.7 and 54.1%, respectively. Compared with the negative control group, ZBH‑1208 barely affected visceral indices or white blood cell count. Furthermore, the expression levels of p53, p21, cyclin‑dependent kinase 7 (CDK7), Wee1, phosphorylated (p)‑cell division cycle 2 (CDC2) (Tyr15), p‑CDC2 (Thr161) and cyclin B1 proteins were upregulated, whereas the expression levels of cyclin E were downregulated, and those of CDC2, CDK2 and CDC25C were barely altered. In conclusion, the present study demonstrated that ZBH‑1208 suppressed the growth of B22 mouse brain tumor xenografts, but did not affect their visceral indices or white blood cell counts. It was suggested that ZBH‑1208 exerted its effects by regulating the expression of p53, p21, Wee1, p‑CDC2 (Tyr15) and cyclin E proteins.

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