Abstract
The resistance of ovarian cancer to platinum-based chemotherapy is a critical issue in the clinical setting. The present study aimed to establish animal models to replicate this clinical condition, as well as to investigate the resistance mechanisms of ovarian cancer. A cisplatin (DDP)-resistant human ovarian cancer cell line, SKOV3/DDP, was screened, validated and injected subcutaneously into the neck of female nude mice. Following tumor establishment, the tumor was collected and cut into small sections, which were subsequently implanted into the ovaries of other nude mice. The growth of the orthotopic tumors was observed and the tumor-bearing mice were sacrificed and dissected. The orthotopic and metastatic tumor tissues were collected, sectioned, stained with hematoxylin and eosin and analyzed. In the present study, 16 nude mice underwent orthotopic transplantation surgery and a tumor model was successfully established in 14/16 of the mice, with an in situ tumor formation rate of 87.5%. Following euthanasia, a laparotomy demonstrated the tumor formation at the site of transplantation, as well as varying degrees of metastasis to additional organs and tissues. Therefore, the present study successfully established an orthotopic tumor transplantation model in nude mice using a c-Kit-positive DDP-resistant human ovarian cancer cell line. This model may represent a useful tool for investigating the resistance mechanism of ovarian cancer, as well as evaluating the efficacy of therapeutic strategies.
Highlights
Ovarian cancer is highly malignant among gynecological tumors and is associated with an insidious onset, rapid progression and a complex early diagnosis, which leads to a poor prognosis and high mortality rates
In a previous clinical study, c‐Kit gene expression was identified to be closely associated with drug resistance and malignancy in ovarian cancer (5), which was consistent with previous findings (4)
The implanted ovarian tumor model exhibited biological characteristics, and a metastatic rate and pattern that were closest to the clinical state
Summary
Ovarian cancer is highly malignant among gynecological tumors and is associated with an insidious onset, rapid progression and a complex early diagnosis, which leads to a poor prognosis and high mortality rates. During clinical treatment, the majority of patients develop a drug resistance (2), which manifests as a tolerance to the chemotherapeutic agents or recurrence following treatment, leading to chemotherapy failure and a marked limitation of this treatment modality (3). Previous clinical studies have shown that malignant ovarian cancer cells express the proto‐oncogene, c‐Kit and that the prognosis of patients exhibiting positive c‐Kit gene expression is usually poorer. The present study used a DDP‐resistant cell line with a high expression of c‐Kit to establish an orthotopic transplantation animal model, stimulating human ovarian cancer with regard to onset, location, mechanism and histological and biological characteristics, was used to investigate association between c‐Kit gene expression and drug resistance and degree of malignancy in ovarian cancer
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