Recombinant human calcineurin B inhibits orthotopic hepatocellular carcinoma xenograt growth in mice by promoting apoptosis

Xiao-Dian Zhang; Zhi-Hui He; Li-Ping Zheng; Guo-Hui Yi; Min-Ge Lin; Li-Zhen Fu; Shu-Hong Tian; Hong-Hai Li; Yan-Da Lu; Shen-Hong Gu; Shao-Jiang Zheng

doi:10.4103/1995-7645.271978

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ORIGINAL ARTICLE

Year : 2019 \| Volume : 12 \| Issue : 14 \| Page : 32-40

Recombinant human calcineurin B inhibits orthotopic hepatocellular carcinoma xenograt growth in mice by promoting apoptosis Xiao-Dian Zhang¹, Zhi-Hui He², Li-Ping Zheng², Guo-Hui Yi³, Min-Ge Lin², Li-Zhen Fu⁴, Shu-Hong Tian¹, Hong-Hai Li², Yan-Da Lu², Shen-Hong Gu¹, Shao-Jiang Zheng⁵ ¹ Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Provincial Center for Drug Safety Evaluation and Research, Hainan Medical University, Haikou 571199, P.R. China ² Tumor Institute, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, P.R. China ³ Public Research Laboratory, Hainan Medical University, Haikou 571199, P.R. China ⁴ Department of Internal Medicine, the Second Affiliated Hospital of Hainan Medical University, Haikou 570203, P.R. China ⁵ Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Provincial Center for Drug Safety Evaluation and Research, Hainan Medical University, Haikou; Tumor Institute, the First Affiliated Hospital of Hainan Medical University, Haikou 570102; Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences, Hainan Medical University, Haikou 571199, P.R. China Correspondence Address: Shao-Jiang Zheng Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Provincial Center for Drug Safety Evaluation and Research, Hainan Medical University, 3 Xueyuan Road, Longhua District, Haikou, 571199 P.R. China Shen-Hong Gu Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Provincial Center for Drug Safety Evaluation and Research, Hainan Medical University, 3 Xueyuan Road, Longhua District, Haikou, 571199 P.R. China Source of Support: None, Conflict of Interest: None DOI: 10.4103/1995-7645.271978

Objective: To explore the effects of recombinant human calcineurin B (rhCNB) on hepatocellular carcinoma in mice. Methods: An in vivo mouse model with hepatocellular carcinoma was established, and the mice were randomized into the rhCNB, positive control and vehicle treatments groups. Tumor growth was assessed via bioluminescence using a small animal imaging system. Relative tumor proliferation rate and tumor growth inhibition were calculated. The expression of p53 and caspase-9 proteins in tumors were detected by immunohistochemistry. In vitro, flow cytometry was used to quantify the cell-cycle stages and rate of apoptosis. Western blotting and quantitative real-time PCR assays were used to evaluate the effects of rhCNB on protein and gene expression of CDK1, cyclin B1, p53 and caspase-9. Results: rhCNB at the higher dose significantly reduced tumor growth in vivo and caused tumor cell apoptosis in vitro. The rhCNB at the higher dose was as effective as cisplatin, and was safer. Conclusions: rhCNB has potent pro-apoptotic effects on tumor cells in vivo and in vitro and is well tolerated in vivo.



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