Establishment of two ovarian cancer orthotopic xenograft mouse models for in vivo imaging: A comparative study

Abstract

Orthotopic tumor animal models are optimal for preclinical research of novel therapeutic interventions. The aim of the present study was to compare two types of ovarian cancer orthotopic xenograft (OCOX) mouse models, i.e. cellular orthotopic injection (COI) and surgical orthotopic implantation (SOI), regarding xenograft formation rate, in vivo imaging, tumor growth and metastasis, and tumor microenvironment. The tumor formation and progression were monitored by bioluminescent in vivo imaging. Cell proliferation and migration abilities were detected by EdU and scratch assays, respectively. Expression of α-SMA, CD34, MMP2, MMP9, vimentin, E-cadherin and Ki67 in tumor samples were detected by immunohistochemistry. As a result, we successfully established COI- and SOI-OCOX mouse models using ovarian cancer cell lines ES2 and SKOV3. The tumor formation rate in the COI and SOI models were 87.5 and 100%, respectively. Suspected tumor cell leakage occurred in 37.5% of the COI models. The SOI xenografts grew faster, held larger primary tumors, and were more metastatic than the COI xenografts. The migration and proliferation properties of the cells that generated SOI xenografts were significantly starker than those deriving COI xenografts in vitro. The tumor cells in SOI xenografts exhibited a mesenchymal phenotype and proliferated more actively than those in the COI xenografts. Additionally, compared with the COI tumors, the SOI tumors contained more cancer associated fibroblasts, matrix metallopeptidase 2 and 9. In conclusion, SOI is a feasible and reliable technique to establish OCOX mouse models mimicking the clinical process of ovarian cancer growth and metastasis, although SOI is more technically difficult and time-consuming than COI.

Tumor cell‑fibroblast heterotypic aggregates in�malignant ascites of patients with ovarian cancer

“…The SKOV3 human EOC cell line was purchased from the China Center for Type Culture Collection. A previously generated subline marked with green fluorescent protein (SKOV3-GFP) was also used (19). For MCA formation, tumor cells (SKOV3 or primary ascitic tumor cells) were seeded into 6-well low-adherence plates (cat.…”

Preparation, characterization, in vitro and in vivo anti-tumor effect of thalidomide nanoparticles on lung cancer

“…In our study, we selected an SX model to evaluate the anticancer effects of THA-NPs. 40,41 Compared to equivalent doses of THA, the use of THA-NPs resulted in a longer median survival time in mice as is shown in Figure 4B (P,0.05). This further illustrates that THA encapsulated in THA-NPs was more effective than free THA in the treatment of lung cancer-bearing mice.…”

Vitamin D Suppresses Ovarian Cancer Growth and Invasion by Targeting Long Non-Coding RNA CCAT2

“…Based on these PK studies, it will be useful to perform in vivo efficacy study to determine the effects of calcitriol against tumor growth and metastasis in subcutaneous or orthotopic xenograft mouse models. To this end, an orthotopic ovarian cancer mouse model would be the most suitable to evaluate the anti-metastasis activity of calcitriol [43,44]. In addition, to reach a higher drug concentration in the tumor site, drug delivery systems, such as nanoparticles or micelle, could be applied to improve the solubility of calcitriol and delivery to the tumors [45,46].…”