Establishment and Characterization of Patient Derived Gastric Cancer Cell Lines

doi:10.3969/j.issn.1674-5817.2017.04.001

Abstract

Abstract: Objective To establish and characterize primary gastric cancer cell lines derived from gastric cancer patient-derived xenograft (PDX) models. Methods Tumors from 12 stable gastric cancer PDX models were selected to establish primary tumor cell lines when the tumor volume reached 500~900 mm³. The established cell lines were characterized by cell morphology, chromosome, STR and immunohistochemical analyses, in vivo tumorigenicity, as well as drug sensitivity in vitro and in vivo. Results Six primary gastric tumor cell lines were successfully established. GAXC031 and GAXC066 were selected and characterized thoroughly. STR analysis confirmed that these 2 cell lines were consistent with their parental PDX models. These 2 cell lines presented the morphological, histological and genomic characteristics of malignant gastric cancer cells. They generated xenograft readily in nude mice and these tumors maintained histology characteristics of the parental PDX tumors. Moreover, compared to the parental PDX models, these 2 cell lines initiated xenografts with higher take rate, shorter incubation period, and better uniformity in tumor growth. In vitro and in vivo drug sensitivity test showed that GAXC031 was more sensitive to 5-fluorouracil than that of GAXC066, while both cell lines were sensitive to cisplatin. Conclusions Six patient derived gastric cell lines were successfully established from PDX models in this study. Deep characterization showed that these cell lines maintained many characteristics of the original PDX models with improved take rate, latent period and uniformity, therefore represent useful tools in basic research and drug screening.

Key words: Patient-derived xenograft (PDX), Gastric cancer, Cell lines, Biological characteristics, Drug efficacy study

CLC Number:

Q95-33

GE Xiao-mei, ZHANG Yi-xin, XIE Fu-bo, LIU Ji-bin, YANG Lei, QU Ying-ying, GU Ying, Li Xue-ting, YANG Wei-min, LIU Xi-peng, ZHOU He, QIANG Fu-lin. Establishment and Characterization of Patient Derived Gastric Cancer Cell Lines[J]. Laboratory Animal and Comparative Medicine, 2017, 37(4): 257-265.

References

[1] Cidon EU, Centeno RG, Lagarto EG, et al.HER-2 evaluation in a specific gastric cancer population with the highest rate of mortality in Spain[J]. J Oncol, 2011:391564
[Epub2011 Oct 27].
[2] Ye H, Jing YF, Shu DX.Can the incidence of gastric cancer be reduced in the new century[J]. J Digest Dis, 2013, 14(1):11-15.
[3] Jemal A, Bray F, Center MM, et al.Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
[4] He YT, Hou J, Chen ZF, et al.Trends in incidence of esophageal and gastric cardia cancer in high-risk areas in China[J]. Eur J Cancer Prev, 2008, 17(2):71-76.
[5] Jin H, Pinheiro PS, Callahan KE, et al.Examining the gastric cancer survival gap between Asians and whites in the United States[J]. Gastric Cancer, 2016 [Epub ahead of print].
[6] 刘天艺, 焦宇飞. 胃黏膜活检标本中上皮内瘤变及早期癌的病理诊断[J]. 中华病理学杂志, 2014, 43(9):644-646.
[7] 王江红, 项颖. 早期胃癌的筛查现状及诊断进展[J]. 重庆医学, 2009, 38(20):2634-2636.
[8] Dan Liu, Ming Lu, Jian Li, et al.The patterns and timing of recurrence after curative resection for gastric cancer in China[J]. World J Surg Oncol, 2016, 14(1), 305.
[9] Binn M, Ruskonéfourmestraux A, Lepage E, et al.Surgical resection plus chemotherapy versus chemotherapy alone: comparison of two strategies to treat diffuse large B-cell gastric lymphoma[J]. Ann Oncol, 2003, 14(12):1751-1757.
[10] Moelans CB, Milne AN, Morsink FH, et al.Low frequency of HER2 amplification and overexpression in early onset gastric cancer[J]. Cell Oncol (Dordr), 2011, 34(2):89-95.
[11] Liu KH, Hung CY, Lu CH, et al.Survival outcomes of geriatric patients with clinically resectable gastric cancer: to operate or not[J]. J Surg Res, 2016, 206(2):481-489.
[12] Thiel A.Targeted therapy in gastric cancer[J]. APMIS, 2015, 123(5):365-372.
[13] Li C, Zou J, Zheng G, et al.MiR-30a Decreases Multidrug Resistance (MDR) of Gastric Cancer Cells[J]. Med Sci Monit, 2016, 22:4509-4515.
[14] Tang QF, Sun J, Yu H, et al.The Zuo Jin Wan formula induces mitochondrial apoptosis of cisplatin-resistant gastric cancer cells via Cofilin-1[J]. Evid Based Complement Alternat Med, 2017, 2017(1):8203189.
[15] 许春花, 杨磊, 汤旭蓁,等. 人源性胃癌移植瘤模型的初步建立及其评价[J]. 实验动物与比较医学, 2014, 34(4): 259-265.
[16] 崔晋峰, 赵晨燕, 曹立勇,等. 食管胃交界腺癌和远端胃癌KLF4SP1及CyclinD1表达的对比研究[J]. 中国肿瘤临床, 2014, 41(2):108-112.
[17] 李平. 浅谈胃癌的中医药治疗[J]. 中医药临床杂志, 2011, 23(3):207-208.
[18] Terashima M, Irinoda T, Fujiwara H, et al.Roles of thymidylate synthase and dihydropyrimidine dehydrogenase in tumor progression and sensitivity to 5-fluorouracil in human gastric cancer[J]. Anticancer Res, 2002, 22(2A):761-768.
[19] Qin B, Tanaka R, Shibata Y, et al.In-vitro schedule-dependent interaction between oxaliplatin and 5-fluorouracil in human gastric cancer cell lines[J]. Anticancer Drugs, 2006, 17(4):445-453.
[20] Zhang X Q, Zhang H M, Sun X E, et al.Inhibitory effects and mechanism of 5-fluorouracil combined with celecoxib on human gastric cancer xenografts in nude mice[J]. Exp Ther Med, 2015, 9(1):105-111.
[21] Chabner BA.NCI-60 Cell Line Screening: A Radical Departure in its Time[J]. J Natl Cancer Inst, 2016, 108(5).