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Stevioside inhibits colorectal cancer progression by regulating macrophage polarization
Yang Bai1, Yuefei Wang1, Fang Zhang1
1Department of Large Intestine, The First School of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Abstract:
ObjectiveThe study aimed to explore the inhibitory effect of stevioside on colorectal cancer and its molecular mechanism.MethodsColorectal cancer cells were selected for functional testing, including the following groups: 0 μM stevioside, 1 μM stevioside, 2.5 μM stevioside and 5 μM stevioside. CCK-8 kit and EdU staining were employed to assess the cell viability. Cell apoptosis was deterred by flow cytometry. Western blot assay was utilized to detect the protein expressions of cleaved-caspase-3, Bax, Bcl-2, E-cadherin and Vimentin. The polarization of macrophage was evaluated through flow cytometry, western blot and immunofluorescence staining. The effect of stevioside on the proliferation of tumor tissue was detected by tumor formation and immunohistochemical staining in nude mice.ResultsStevioside exhibited a significant concentration-dependent inhibitory effect on the proliferation, migration, and invasion of colorectal cancer cells, while promoting apoptosis in vitro. Following stevioside treatment, there was a notable reduction in tumor volume and weight observed. Flow cytometry and immunohistochemical staining results showed that compared with control group, CD86+ cell ratio was increased in stevioside treatment group, while the CD206+ cell ratio was decreased in stevioside treatment group. RT-qPCR analysis revealed that, compared to the control group, stevioside treatment significantly reduced the mRNA expressions of Arg-1 and IL-10, while concomitantly increasing the mRNA expressions of IL-12 and TNF-α in a concentration-dependent manner.ConclusionStevioside possesses the ability to significantly hinder the proliferation of colorectal cancer cells and induce apoptosis, the mechanism of which may be closely related to the regulation of macrophage M1 polarization.
Insights
Stevioside effectively inhibits colorectal cancer cell proliferation and migration while promoting apoptosis. This natural compound may also regulate macrophage polarization, offering a potential therapeutic avenue for colorectal cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide.
- Identifying novel therapeutic agents with fewer side effects is crucial for CRC treatment.
- Stevioside, a natural sweetener, has shown potential anti-cancer properties in preliminary studies.
Purpose of the Study:
- To investigate the inhibitory effects of stevioside on colorectal cancer (CRC) progression.
- To elucidate the underlying molecular mechanisms, including its impact on cell apoptosis and macrophage polarization.
Main Methods:
- Functional assays including CCK-8 and EdU staining assessed cell viability and proliferation.
- Flow cytometry and Western blot analyzed apoptosis and protein expression (cleaved-caspase-3, Bax, Bcl-2, E-cadherin, Vimentin).
- Macrophage polarization was evaluated using flow cytometry, Western blot, immunofluorescence, and RT-qPCR (Arg-1, IL-10, IL-12, TNF-α). Tumor formation in nude mice was also assessed.
Main Results:
- Stevioside demonstrated a concentration-dependent inhibition of CRC cell proliferation, migration, and invasion, alongside enhanced apoptosis in vitro.
- In vivo studies showed reduced tumor volume and weight following stevioside treatment.
- Stevioside treatment promoted M1 macrophage polarization, evidenced by increased CD86+ cells and decreased CD206+ cells, along with altered mRNA expression of key cytokines (IL-12, TNF-α increased; Arg-1, IL-10 decreased).
Conclusions:
- Stevioside exhibits significant anti-cancer activity against colorectal cancer by inhibiting proliferation and inducing apoptosis.
- The mechanism involves the modulation of macrophage M1 polarization, suggesting a potential immunotherapeutic role for stevioside in CRC treatment.
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