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Antiangiogenic therapy using sunitinib combined with rapamycin retards tumor growth but promotes metastasis
Tao Yin1, Sisi He1, Tinghong Ye1
1State Key Laboratory of Biotherapy, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Background:
This study investigated the synergistic effect of sunitinib and rapamycin on tumor growth and metastasis in murine breast cancer model.
Methods:
The synergistic antitumor effect of sunitinib and rapamycin on tumor growth and metastasis was investigated. Myeloid-derived suppressor cells (MDSCs) in spleens and lungs were assessed. Tumor hypoxia, vessel density and micrometastasis were evaluated. Versican, indoleamine 2,3-dioxygenase (IDO), arginase 1, interleukin-6 (IL-6), IL-10, and transforming growth factor β (TGF-β) in the lungs and tumors were examined. IL-6 and TGF-β in the blood were evaluated.
Results:
Synergism between sunitinib and rapamycin on tumor growth was observed. Sunitinib plus rapamycin reduced splenomegaly, MDSCs in spleens and lungs, and microvessel density in tumor microenvironment, while exacerbated hypoxia and promoted cancer lung metastasis. Sunitinib plus rapamycin markedly induced versican, IDO, arginase 1, IL-6, and TGF-β expression in the lungs, whereas it reduced IDO and IL-10 expression in the primary tumor tissues. IL-6 levels in the circulation were increased after rapamycin and combination therapies.
Conclusions:
The combination of sunitinib plus rapamycin reduced the tumor growth but promoted tumor metastasis. This study warrants that further mTOR inhibition treatment should be closely watched in clinical setting, especially combined with antiangiogenic therapy.
Insights
Sunitinib and rapamycin combination therapy reduced breast cancer growth but worsened lung metastasis. This suggests careful monitoring of mTOR inhibition, especially with antiangiogenic treatments, is crucial in clinical settings.
Area of Science:
- Oncology
- Cancer Research
- Pharmacology
Background:
- Investigated the synergistic effects of sunitinib and rapamycin in a murine breast cancer model.
- Focused on understanding the impact on tumor growth and metastasis.
Purpose of the Study:
- To evaluate the combined efficacy of sunitinib and rapamycin on tumor progression.
- To analyze the effects on the tumor microenvironment, immune cells, and metastatic potential.
Main Methods:
- Assessed myeloid-derived suppressor cells (MDSCs), tumor hypoxia, and microvessel density.
- Quantified expression of versican, indoleamine 2,3-dioxygenase (IDO), arginase 1, IL-6, IL-10, and TGF-β in tumors and lungs.
- Monitored IL-6 and TGF-β levels in circulation.
Main Results:
- Combination therapy reduced tumor growth, splenomegaly, MDSCs, and microvessel density.
- Exacerbated tumor hypoxia and promoted lung metastasis.
- Induced specific molecular changes in lungs and primary tumors, with increased IL-6 in circulation.
Conclusions:
- Sunitinib plus rapamycin inhibited tumor growth but enhanced metastasis.
- Highlights the need for caution with mTOR inhibitors, particularly when combined with antiangiogenic therapies, in clinical practice.
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