Initially Establishment and Characterization of Patient Derived Gastric Cancer Xenograft Models

doi:10.3969/j.issn.1674-5817.2014.04.001

Abstract

Abstract: Objective To establish the patient derived gastric cancer xenografts by subcutaneous implantation of clinical gastric cancer specimens in immunodeficient mice, and assess its characters. Methods Ninety-eight fresh human gastric cancer specimens were subcutaneously implanted into SCID mice. They were serially passaged with BALB/c-nu/nu mice when the xenograft tumors reached size 500~1000 mm³. Tumors were cryoperserved in liquid nitrogen for future model recovery, and also snap frozen, paraffin-embedded for future analysis. H&E staining and pathological analyses were also performed. Twelve selected patient derived gastric cancer xenograft models were evaluated by in vivo efficacy studies and in vitro chemo sensitivity studies. Results 25 gastric cancer xenografts successfully developed into tumor and could be continuously passaged to next generations, the engraftment efficency is 25.52%. These xenografts showed similar histological features compared with the original clinical specimen. Efficacy studies in vivo showed individual differences in sensitivity to 5-FU and cisplatin among different models: 2 xenografts were highly inhibited by 5-FU (TGI>60%), the same treatment is less effective in the other 10 xenografts; 3 xenografts were completely inhibited by cisplatin (TGI>100%), 4 xenografts were highly inhibited by cisplatin (TGI, 60%-90%), and 5 other xenografts were relatively insensitive to cisplatin treatment (TGI<60%). Chemo sensitivity studies in vitro were performed with 3 representative models, their sensitivity to 5-FU is GAX001(IC₅₀:3.187 μmol) > GAX007(IC₅₀:6.886 μmol) > GAX027(IC₅₀:8.323 μmol), and their sensitivity to cisplatin is GAX027(IC₅₀:2.753 μmol) > GAX001(IC₅₀:3.211 μmol) > GAX007(IC₅₀:8.137 μmol). Conclusions 25 Patient derived gastric cancer xenograft models were successfully established. The transplanted tumors showed similar histological features compared with the original clinical specimen. From the results of the 12 efficacy study, the xenografts showed differently sensitivity to different chemotherapy, representing different chemo-responses in the clinic. These gastric cancer models are valuable for anti-cancer drug development and research

Key words: Gastric cancer, Patient derived xenograft model, Cancer model, Subcutaneous transplantation, Anti-cancer drugs

CLC Number:

Q95-33

XU Chun-hua, YANG Lei, TANG Xu-zhen, HU Gang, GENG Qin, OU YANG Ke-dong, XIE Fu-bo, WANG Ke, QIN Xiao-ran, LIU Ji-bin, YANG Wei-min, TAO Wei-kang, ZHANG Yi-xin, ZHOU He. Initially Establishment and Characterization of Patient Derived Gastric Cancer Xenograft Models[J]. Laboratory Animal and Comparative Medicine, 2014, 34(4): 259-265.

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