Lab Anim Res.  2010 Dec;26(4):369-375. 10.5625/lar.2010.26.4.369.

The Incidence Rate and Severity of Orthotopic Lung Cancer in an Animal Model Depends on the Number of A549 Cells and Transplantation Period

• Lee J
• Han YA
• Yang HS
• Song JA
• Yang YS
• Kwon S
• Kang MS
• Lee K
• Heo JD
• Cho KH
• Song CW

• KMID: 2114705
• DOI: http://doi.org/10.5625/lar.2010.26.4.369

Abstract

The incidence rate of lung cancer is continually increasing, and lung cancer is the leading cause of cancer-related death worldwide. Nevertheless, few therapeutic methods are available for lung cancer. Therefore, establishing appropriate lung cancer animal models is important to investigate mechanisms and to evaluate new drugs for lung cancer. In the present study, we transplanted non-small cell lung cancer A549 human adenocarcinoma cells (2x10(4), 2.0x10(5), and 2.0x10(6) cells) into the right lobe of BALB/c nude mice via the intercostal space to develop an orthotopic lung cancer animal model that is minimally invasive and similar to human lung cancer. We then investigated the incidence rate and severity of lung cancer according to the A549 cell number (2x10(4), 2.0x10(5), and 2.0x10(6) cells) and transplantation periods (4~23 days). Lung cancer development was confirmed with gross examination, which was supported by histopathological examination. These results indicate that the incidence rate and severity of lung cancer was increased depending on the number of transplanted cells and transplantation period which the cell number and duration are increasing risk of lung cancer. Thus, this study can provide appropriate reference data to develop an orthotopic lung cancer animal model using the non-small cell lung cancer A549 cell line for researching mechanisms and evaluating candidate drugs, including various approaches for treating lung cancer.

Keyword

Lung cancer animal model; orthotopic; A549

MeSH Terms

Adenocarcinoma
Animals
Carcinoma, Non-Small-Cell Lung
Cell Count
Cell Line
Humans
Incidence
Lung
Lung Neoplasms
Mice
Mice, Nude
Models, Animal
Transplants

Figure

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  Figure 1. Study design of an orthotopic lung cancer mouse model. (A) A549 adenocarcinoma cells (2.0×104) were transplanted into BALB/c nude mice. (B) A549 adenocarcinoma cells (2.0×105 and 2.0×106) were transplanted into BALB/c nude mice.

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  Figure 2. Histopathological observation of the lung tissue. (A) Saline was injected into BALB/c nude mice at day 22. (B) A549 adenocarcinoma cells (2.0×106) were transplanted into BALB/c nude mice at day 22.

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  Figure 3. Gross examination after transplantation of A549 adenocarcinoma cells, indicates that the severity of lung cancer (arrow) depends on the number of transplanted cells. (A) Saline was injected into BALB/c nude mice at day 22. (B) A549 adenocarcinoma cells (2.0×104) were transplanted into BALB/c nude mice at day 23. (C) A549 adenocarcinoma cells (2.0×105) were transplanted into BALB/c nude mice at day 22. (D) A549 adenocarcinoma cells (2.0×106) were transplanted into BALB/c nude mice at day 22.

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  Figure 4. Histopathological examination after transplantation of A549 adenocarcinoma cells indicates that the severity of lung cancer (star) depends on the number of transplanted cells. (A) Saline was injected into BALB/c nude mice at day 22. (B) A549 adenocarcinoma cells (2.0×104) were transplanted into BALB/c nude mice at day 23. (C) A549 adenocarcinoma cells (2.0×105) were transplanted into BALB/c nude mice at day 22. (D) A549 adenocarcinoma cells (2.0×106) were transplanted into BALB/c nude mice at day 22.

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  Figure 5. Gross examination after transplantation of A549 adenocarcinoma cells indicates that the severity of lung cancer (arrow) depends on the number of transplantation days. (A) Saline was injected into BALB/c nude mice at day 22. (B) A549 adenocarcinoma cells (2.0×106) were transplanted into BALB/c nude mice at day 8. (C) A549 adenocarcinoma cells (2.0×106) were transplanted into BALB/c nude mice at day 15. (D) A549 adenocarcinoma cells (2.0×106) were transplanted into BALB/c nude mice at day 22.

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  Figure 6. Tumor area in histopathological slides depends on the number of transplanted A549 adenocarcinoma cells and transplanted days (mean±SE). Tumor area depends on transplanted days was significantly different (P<0.05). n=5∼6.

Reference

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