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Updated: Jun 13, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
TRAIL and doxorubicin combination induces proapoptotic and antiangiogenic effects in soft tissue sarcoma in vivo
Suizhao Wang1, Wenhong Ren, Jeffery Liu
1Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Purpose:
Novel therapeutic approaches for complex karyotype soft tissue sarcoma (STS) are crucially needed. Consequently, we assessed the efficacy of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in combination with chemotherapy, on local and metastatic growth of human STS xenografts in vivo.
Experimental Design:
TRAIL was evaluated alone and combined with low-dose doxorubicin in two human STS severe combined immunodeficient mouse xenograft models using fibrosarcoma (HT1080; wild-type p53) and leiomyosarcoma (SKLMS1; mutated p53), testing for effects on local growth, metastasis, and overall survival. Magnetic resonance imaging was used to evaluate local growth and bioluminescence was used to longitudinally assess lung metastases. Tissues were evaluated through immunohistocemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining for treatment effects on tumor cell proliferation, apoptosis, angiogenesis, angiogenic factors, and TRAIL receptor expression. Quantitative real-time polymerase chain reaction (QRTPCR) angiogenesis array was used to assess therapy-induced gene expression changes.
Results:
TRAIL/doxorubicin combination induced marked STS local and metastatic growth inhibition in a p53-independent manner. Significantly increased (P < 0.001) host survival was also demonstrable. Combined therapy induced significant apoptosis, decreased tumor cell proliferation, and increased TRAIL receptor (DR4 and DR5) expression in all treated tumors. Moreover, decreased microvessel density was observed, possibly secondary to increased expression of the antiangiogenic factor CXCL10 and decreased proangiogenic interleukin-8 cytokine in response to TRAIL/doxorubicin combination, as was also observed in vitro.
Conclusions:
Given the urgent need for better systemic approaches to STS, clinical trials evaluating TRAIL in combination with low-dose chemotherapy are potentially warranted.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combined with doxorubicin effectively inhibited soft tissue sarcoma (STS) growth and metastasis in mice. This novel combination therapy also improved survival, offering a promising new treatment strategy for STS.
Area of Science:
- Oncology
- Cancer Therapeutics
- Sarcoma Research
Background:
- Soft tissue sarcoma (STS) presents complex karyotype challenges, necessitating novel therapeutic strategies.
- Current treatments for STS often have limitations, driving the search for more effective systemic approaches.
Purpose of the Study:
- To evaluate the efficacy of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combined with chemotherapy against local and metastatic growth of human STS xenografts.
- To assess the impact of TRAIL and doxorubicin combination therapy on tumor progression and host survival in preclinical STS models.
Main Methods:
- Two human STS xenograft models (fibrosarcoma HT1080 and leiomyosarcoma SKLMS1) were used to test TRAIL alone and combined with low-dose doxorubicin.
- Tumor growth, metastasis, and survival were monitored using MRI and bioluminescence; tissue analysis included apoptosis, proliferation, angiogenesis, and receptor expression.
- Quantitative real-time PCR assessed therapy-induced gene expression changes related to angiogenesis.
Main Results:
- The TRAIL/doxorubicin combination significantly inhibited local and metastatic STS growth in a p53-independent manner.
- Combined therapy led to increased apoptosis, reduced tumor cell proliferation, and elevated TRAIL receptor expression (DR4 and DR5).
- Decreased microvessel density was observed, potentially due to altered expression of angiogenic factors like CXCL10 and interleukin-8.
Conclusions:
- TRAIL in combination with low-dose chemotherapy demonstrates significant potential for treating soft tissue sarcoma.
- The findings support the initiation of clinical trials to evaluate this combination therapy for STS patients.
- This approach offers a promising new avenue for managing STS, addressing the need for improved systemic treatments.
