Establishment of a Jaw Fibrosarcoma Patient-Derived Xenograft and Evaluation of the Tumor Suppression Efficacy of Plumbagin Against Jaw Fibrosarcoma

Abstract

Background: Head and neck fibrosarcoma is a rare malignant tumor, accounting for about 1% of all head and neck tumors. It can also occur in the jaw bone, for which surgical resection is the main treatment but the recurrence rate is high and the prognosis is usually poor. Due to the lack of models mimicking the biological characteristics of the tumor, there is little progress in the research of the pathogenesis and treatment of fibrosarcoma. Therefore, there is an urgent need to explore a high-fidelity model that can reflect the biological characteristics of fibrosarcoma for the sake of improving the therapeutic outcome and prognosis, and preventing recurrence. Patient-derived xenografts (PDX) may more accurately reflect the human disease, and is an attractive platform to study disease biology and develop treatments and biomarkers. In this study we describe the establishment of jaw fibrosarcoma PDX models and compare PDX tumors to those of human origin. Methods: Tumor biopsies from a patient with jaw fibrosarcoma were implanted in immunodeficient mice. Primary and PDX tumors were characterized extensively by histology, immunohistochemistry and humanized identification. Based on the finding of our previous preliminary research that plumbagin had an anti-tumor effect against head and neck cancer, we used this model in the present study to evaluate the anti-tumor effect of plumbagin on jaw fibrosarcoma. Results: The established PDX model maintained the histological and immunohistochemical characteristics of the primary tumor. Plumbagin significantly inhibited the tumor growth in the jaw fibrosarcoma PDX model. Conclusion: We successfully established a PDX model of jaw fibrosarcoma and demonstrated that this PDX model preserved the important molecular characteristics of the human primary tumor, thus providing a powerful tool for treatment research and new drug development of jaw fibrosarcoma. In addition, plumbagin was found to have an inhibitory effect on the growth of PDX modeled jaw fibrosarcoma, which provides a preliminary research basis for its clinical application.

Novel pyroptosis-associated genes signature for predicting the prognosis of sarcoma and validation

“…The prognosis is poor. Histological biopsy is the most authoritative standard for the diagnosis of Sarcoma [ 34 , 35 ]. The main therapeutic methods are radiation therapy and surgery [ 36 ], and there are still no proven target drugs for sarcomas.…”

Novel pyroptosis-associated genes signature for predicting the prognosis of Sarcoma

“…The prognosis is poor. Histological biopsy is the most authoritative standard for the diagnosis of Sarcoma [34,35]. The main therapeutic methods are radiation therapy and surgery [36], and there are still no proven target drugs for sarcomas.…”

Plumbagin has an inhibitory effect on the growth of TSCC PDX model and it enhances the anticancer efficacy of cisplatin

“…When the tumor volume grew to more than 1,000 mm 3 , the tumor was resected and cut into 2 mm × 2 mm × 2 mm (8 mm 3 ) sections, subcutaneously were inoculated into the scapular region of BALB/c nude mice, numbered P1, and the tumors were passaged to P4 by the same method and used for subsequent experimental research. The implantation procedure was carried out as previously described [ 28 ].…”