Application of <i>in vivo</i> imaging system to establish and evaluate an experimental mouse model of lung cancer_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

CHEN Zhengju ¹ , GU Qiumei ¹ , XU Chunyan ¹ , LIU Zhiqiang ² , SHEN Meiling ¹ ,  SUN Huaiqiang ¹

1. Research Core Facilities, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Precision Medicine Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

SUN Huaiqiang, Email: sunhuaiqiang@scu.edu.cn

Keywords：

Orthotopic lung cancer model; In vivo imaging system; A549 cells

DOI：

10.7507/1671-6205.202105060

Video：

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Objective To monitor the importance of establishing lung cancer models for immunological treatment through in vivo imaging system (IVIS). Methods In this study, a new optical bioluminescence IVIS was used to confirm the tumour formation and luminescence in male BALB/c nude mice by injecting A549-luc cells. First, A549-luc cells which expressed luciferase stably were transferred into nude mice by tail vein injection in order to establish a stable and reliable model of lung cancer. Then, D-fluorescein potassium salt was intraperitoneally injected every other week. The tumor formation and growth were dynamically observed on day 7^th, 14^th and 21^st by IVIS Spectrum and pathological exam with hematoxylin-eosin staining. Results Animal model of lung cancer was successfully established, and the development of lung cancer was effectively monitored by IVIS real-time fluorescence value which was consistent with pathological exam, and tumor volume was correlated with fluorescence intensity (r=0.7996, P<0.01). Conclusions IVIS has multiple benefits, including high sensitivity and specificity, simple operation, and no radiation. IVIS Spectrum can measure the fluorescence of tumor formed by injection of A549-luc cells in nude mice metastasis of lung cancer in a non-invasive, real-time and dynamic mode, which is worthy of promotion for using in clinical research.

Citation： CHEN Zhengju, GU Qiumei, XU Chunyan, LIU Zhiqiang, SHEN Meiling, SUN Huaiqiang. Application of in vivo imaging system to establish and evaluate an experimental mouse model of lung cancer. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(11): 802-806. doi: 10.7507/1671-6205.202105060 Copy

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2.	Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc, 2019, 94(8): 1623-1640.
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7.	胡丽丽, 阮永华. 移植性肺癌动物模型的建立和研究进展. 临床与实验病理学杂志, 2012, 28(8): 906-908.
8.	Lauber DT, Fülöp A, Kovács T, et al. State of the art in vivo imaging techniques for laboratory animals. Lab Anim, 2017, 51(5): 465-478.
9.	Sierakowiak A, Henriques-Normark B, Iovino F. IVIS spectrum CT to image the progression of pneumococcal infections in vivo. Methods Mol Biol, 2019, 1968: 195-202.
10.	Tan X, Luo QL, Zhou SQ, et al. Erchen Plus Huiyanzhuyu decoction inhibits the growth of laryngeal carcinoma in a mouse model of phlegm-coagulation-blood-stasis syndrome via the STAT3/cyclin D1 pathway. Evid Based Complement Alternat Med, 2020, 2020: 2803496.
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14.	Morita N, Haga S, Ohmiya Y, Ozaki M. Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases. Anal Biochem, 2016, 497: 24-26.
15.	Yang WW, Lu Y, Xu YC, et al. Estrogen represses hepatocellular carcinoma (HCC) growth via inhibiting alternative activation of tumor-associated macrophages (TAMs). J Biol Chem, 2012, 287(48): 40140-40149.
16.	Zhang Q, Wang L, Qian Q, et al. Target area extraction algorithm for the in vivo fluorescence imaging of small animals. ACS Omega, 2020, 5(32): 20100-20106.
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19.	刘启才, 郑国兵, 李晓艳, 等. 荧光素酶标记的肺癌细胞系的建立及动物模型验证. 中国现代医学杂志, 2011, 21(35): 4396-4399, 4404.
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21.	郭东勇, 李国友, 徐诚望, 等. 小动物活体成像法评价硝呋替莫对人源性神经母细胞瘤细胞SH-SY5Y肾转移瘤模型裸鼠的治疗作用. 国际药学研究杂志, 2018, 45(11): 858-864.
22.	安国, 许辉, 张文龙, 等. 小动物活体成像系统Spectrum-CT在人肺癌裸鼠原位移植瘤模型建立中的应用. 肿瘤研究与临床, 2020, 32(4): 250-255.
23.	李百慧. PI3 K抑制剂促进肿瘤血管正常化改善阿霉素治疗乳腺癌的研究. 吉林大学, 2019.
24.	王伟, 陈超, 刘延明, 等. 应用小动物活体成像追踪观察EGFP标记的间充质干细胞. 中国细胞生物学学报, 2016, 38(2): 185-192.
25.	罗华灶, 李雪, 依含, 等. 荧光素酶标记小鼠结肠癌细胞建立活体成像移植瘤模型. 中国免疫学杂志, 2019, 35(17): 2106-2111.
26.	王蕾, 王晓英, 王玥, 等. 一种高效慢病毒转染小鼠肺方法的建立. 军事医学, 2019, 43(8): 616-619.
27.	刘凡, 赵玉, 潘新宇, 等. 活体成像技术在NK/T细胞淋巴瘤早期检测中的应用价值研究. 中国全科医学, 2019, 22(30): 3689-3693,3700.

1. Wang YW, Zou SY, Zhao ZY, et al. New insights into small-cell lung cancer development and therapy. Cell Biol Int, 2020, 44(8): 1564-1576.
2. Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc, 2019, 94(8): 1623-1640.
3. Balata H, Fong KM, Hendriks LE, et al. Prevention and early detection for NSCLC: advances in thoracic oncology 2018. J Thorac Oncol, 2019, 14(9): 1513-1527.
4. 周雪瑞, 黄选东. 免疫缺陷动物裸鼠. 生物学教学, 2007, 32(3): 2-4.
5. Malyla V, Paudel KR, Shukla SD, et al. Recent advances in experimental animal models of lung cancer. Future Med Chem, 2020, 12: 567-581.
6. Wang Y, Rouggly L, You M, et al. Animal models of lung cancer characterization and use for chemoprevention research. Prog Mol Biol Transl Sci, 2012, 105: 211-226.
7. 胡丽丽, 阮永华. 移植性肺癌动物模型的建立和研究进展. 临床与实验病理学杂志, 2012, 28(8): 906-908.
8. Lauber DT, Fülöp A, Kovács T, et al. State of the art in vivo imaging techniques for laboratory animals. Lab Anim, 2017, 51(5): 465-478.
9. Sierakowiak A, Henriques-Normark B, Iovino F. IVIS spectrum CT to image the progression of pneumococcal infections in vivo. Methods Mol Biol, 2019, 1968: 195-202.
10. Tan X, Luo QL, Zhou SQ, et al. Erchen Plus Huiyanzhuyu decoction inhibits the growth of laryngeal carcinoma in a mouse model of phlegm-coagulation-blood-stasis syndrome via the STAT3/cyclin D1 pathway. Evid Based Complement Alternat Med, 2020, 2020: 2803496.
11. Lofgren J, Miller AL, Lee CCS, et al. Analgesics promote welfare and sustain tumour growth in orthotopic 4 T1 and B16 mouse cancer models. Lab Anim, 2018, 52(4): 351-364.
12. United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) Guidelines for the Welfare of Animals in Experimental Neoplasia (Second Edition). Br J Cancer, 1998, 77(1): 1-10.
13. Huan Z, Zheng CL, Wang YZ, et al. miR-1323 promotes cell migration in lung adenocarcinoma by targeting Cbl-b and is an early prognostic biomarker. Front Oncol, 2020, 10: 181.
14. Morita N, Haga S, Ohmiya Y, Ozaki M. Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases. Anal Biochem, 2016, 497: 24-26.
15. Yang WW, Lu Y, Xu YC, et al. Estrogen represses hepatocellular carcinoma (HCC) growth via inhibiting alternative activation of tumor-associated macrophages (TAMs). J Biol Chem, 2012, 287(48): 40140-40149.
16. Zhang Q, Wang L, Qian Q, et al. Target area extraction algorithm for the in vivo fluorescence imaging of small animals. ACS Omega, 2020, 5(32): 20100-20106.
17. Shrestha N, Lateef Z, Martey O, et al. Does the mouse tail vein injection method provide a good model of lung cancer?. F1000 Res, 2019, 8: 190.
18. Keppens C, Dequeker EM, Pauwels P, et al. PD-L1 immunohistochemistry in non-small-cell lung cancer: unraveling differences in staining concordance and interpretation. Virchows Arch, 2021, 478(5): 827-839.
19. 刘启才, 郑国兵, 李晓艳, 等. 荧光素酶标记的肺癌细胞系的建立及动物模型验证. 中国现代医学杂志, 2011, 21(35): 4396-4399, 4404.
20. 樊志超. 应用活体流式细胞仪和活体成像技术对肝癌进展与转移的监测及疗效评估研究. 复旦大学, 2013.
21. 郭东勇, 李国友, 徐诚望, 等. 小动物活体成像法评价硝呋替莫对人源性神经母细胞瘤细胞SH-SY5Y肾转移瘤模型裸鼠的治疗作用. 国际药学研究杂志, 2018, 45(11): 858-864.
22. 安国, 许辉, 张文龙, 等. 小动物活体成像系统Spectrum-CT在人肺癌裸鼠原位移植瘤模型建立中的应用. 肿瘤研究与临床, 2020, 32(4): 250-255.
23. 李百慧. PI3 K抑制剂促进肿瘤血管正常化改善阿霉素治疗乳腺癌的研究. 吉林大学, 2019.
24. 王伟, 陈超, 刘延明, 等. 应用小动物活体成像追踪观察EGFP标记的间充质干细胞. 中国细胞生物学学报, 2016, 38(2): 185-192.
25. 罗华灶, 李雪, 依含, 等. 荧光素酶标记小鼠结肠癌细胞建立活体成像移植瘤模型. 中国免疫学杂志, 2019, 35(17): 2106-2111.
26. 王蕾, 王晓英, 王玥, 等. 一种高效慢病毒转染小鼠肺方法的建立. 军事医学, 2019, 43(8): 616-619.
27. 刘凡, 赵玉, 潘新宇, 等. 活体成像技术在NK/T细胞淋巴瘤早期检测中的应用价值研究. 中国全科医学, 2019, 22(30): 3689-3693,3700.

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Chinese Journal of Respiratory and Critical Care Medicine

Application of in vivo imaging system to establish and evaluate an experimental mouse model of lung cancer

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