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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Chitooligosaccharides inhibit tumor progression and induce autophagy through the activation of the p53/mTOR pathway
Zhen Pan1, Dong-Dong Cheng1, Xiao-Juan Wei1
1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Abstract:
Osteosarcoma is the most common primary sarcoma of bone. The use of Chitooligosaccharide (COS) as a drug carrier is an emerging new strategy for cancer therapy. However, the application of COS in osteosarcoma has not been reported. Here, we investigated the influence of COS on osteosarcoma, and suggested the underlying mechanism. Initially, we obtained COS with a low-degree-polymerized (DP = 2-6) by enzymatic hydrolysis. Using these COS materials, in vitro assays showed that COS elicited the anti-tumor activity against osteosarcoma cells. We found that COS had significant effects on cell growth, metastasis inhibition, apoptosis and autophagy induction, and triggered pro-apoptosis autophagy through p53/mTOR signaling pathway in osteosarcoma cells. In addition, the COS also inhibited tumor growth and metastasis in an osteosarcoma xenograft model in vivo. Finally, we showed that COS could increase sensitivity to chemotherapy of cisplatin in vitro. Thus, we provide experimental evidence to demonstrate that COS has anti-tumor effect on osteosarcoma, and COS can be a new potential therapeutic candidate for the treatment of osteosarcoma.
Insights
Chitooligosaccharide (COS) demonstrates significant anti-tumor effects against osteosarcoma cells by inhibiting growth and metastasis. This study suggests COS as a promising therapeutic candidate for osteosarcoma treatment.
Area of Science:
- Oncology
- Biochemistry
- Biomaterials
Background:
- Osteosarcoma is the most common primary bone sarcoma.
- Chitooligosaccharide (COS) is an emerging drug carrier for cancer therapy.
- The therapeutic potential of COS in osteosarcoma remains unexplored.
Purpose of the Study:
- To investigate the anti-tumor effects of Chitooligosaccharide (COS) on osteosarcoma.
- To elucidate the underlying mechanisms of COS action in osteosarcoma.
- To evaluate COS as a potential therapeutic candidate for osteosarcoma.
Main Methods:
- Enzymatic hydrolysis was used to obtain low-degree-polymerized COS (DP = 2-6).
- In vitro assays assessed COS effects on osteosarcoma cell growth, metastasis, apoptosis, and autophagy.
- An in vivo osteosarcoma xenograft model evaluated tumor growth and metastasis inhibition.
- COS's influence on cisplatin chemotherapy sensitivity was examined.
Main Results:
- COS exhibited significant anti-tumor activity against osteosarcoma cells in vitro.
- COS inhibited cell growth and metastasis, and induced apoptosis and autophagy via the p53/mTOR pathway.
- COS administration suppressed tumor growth and metastasis in vivo.
- COS enhanced the efficacy of cisplatin chemotherapy against osteosarcoma.
Conclusions:
- COS possesses notable anti-tumor properties against osteosarcoma.
- COS modulates key cellular pathways involved in cancer progression.
- COS represents a promising novel therapeutic agent for osteosarcoma treatment.
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