International Journal of Molecular Medical Science, 2024, Vol.14, No.6, 324-341 http://medscipublisher.com/index.php/ijmms 333 thereby promoting cell death in tumor cells. Additionally, Sanghuangporus polysaccharides can arrest the cell cycle at specific phases, such as the G0/G1 and S phases, further inhibiting tumor cell proliferation (Shao et al., 2014). Another key mechanism by which Sanghuangporus polysaccharides exert their antitumor effects is through the regulation of the tumor microenvironment. These polysaccharides can modify the immune landscape within tumors, promoting the infiltration and activation of immune cells that target cancer cells. For instance, polysaccharide components such as SSP1 were extracted and isolated from Sanghuangporus derived from mulberry and analyzed for their structure and monosaccharide composition. Network pharmacology and molecular docking analysis revealed that SSP1 might inhibit HepG2 tumor cells through core targets such as VEGFA and AR. These polysaccharides can also enhance the activity of macrophages and T cells, which is crucial for initiating an effective antitumor immune response. This immunomodulatory effect is partially mediated by the antioxidant properties of Sanghuangporus polysaccharides, which reduce the immunosuppressive effects of oxidative stress in the tumor microenvironment (Yu et al., 2021b). Sanghuangporus polysaccharides inhibit tumor growth through a multifaceted approach that involves reducing oxidative stress, inducing apoptosis, arresting the cell cycle, and modulating the tumor microenvironment. These combined actions make Sanghuangporus polysaccharides promising candidates for cancer therapy, particularly in strategies aimed at targeting oxidative stress and enhancing immune responses against tumors. 6 Combined Application of Sanghuangporus Polysaccharides with Conventional Antitumor Drugs 6.1 Antitumor effects of combined drug therapy Sanghuangporus polysaccharides, as the main active components of the medicinal fungus Sanghuangporus, have been shown to effectively inhibit tumor growth and metastasis and induce apoptosis in tumor cells. Additionally, when used in combination with conventional chemotherapy drugs, Sanghuangporus polysaccharides can enhance antitumor effects. The mechanisms involved include modulating immune responses and directly acting on tumor cells, which can improve the efficacy of traditional chemotherapy, leading to better treatment outcomes and reduced side effects. For example, polysaccharides extracted from Sanghuangporus vaninii (SVP) have demonstrated the ability to inhibit tumor cell proliferation, induce apoptosis, and reduce the migration and invasion of cancer cells, particularly in breast cancer models (Wan et al., 2020). When combined with conventional chemotherapy drugs, these polysaccharides enhance antitumor effects by modulating the tumor microenvironment and boosting immune responses (Wang et al., 2022b; Li et al., 2023). Studies have shown that natural polysaccharides, including those fromSanghuangporus, can significantly increase the efficacy of chemotherapy drugs such as cisplatin in ovarian cancer by inhibiting cell proliferation, inducing apoptosis, and enhancing immunomodulatory activities (Wang et al., 2022b). This synergistic effect not only improves the antitumor efficacy but also helps in mitigating the adverse effects commonly associated with chemotherapy, making the treatment more tolerable for patients. 6.2 Molecular mechanisms of combined drug therapy The molecular mechanisms underlying the enhanced antitumor effects of combined therapy involving Sanghuangporus polysaccharides and conventional drugs are multifaceted. One of the key mechanisms is the activation of the p53 signaling pathway, which plays a crucial role in regulating cell cycle arrest and apoptosis. SVP, for example, has been shown to enhance the activation of p53-related genes and down-regulate matrix metalloproteinase (MMP) expression, thereby inhibiting tumor growth and metastasis (Wan et al., 2020). Additionally, polysaccharides can modulate the tumor microenvironment by enhancing the immune response. They activate both non-specific and specific immune responses, leading to the inhibition of tumor proliferation and metastasis (Figure 7) (Ying and Hao, 2023). Polysaccharides also improve the delivery and efficacy of chemotherapy drugs through the use of stimulus-responsive nanomedicines, which allow for controlled drug
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