Merging Nhird and Basic Study to Create the Novel Screening Platform of Anti-Prostate Cancer Herbs-The Role and Mechanism of Astragalus Polysaccharides on Pd-1/Pd-L1 Immunotherapy and Ferroptosis of Prostate Cancer

Because National Health Insurance (NHI) program of Taiwan reimburses claims for Chinese medicine, the Taiwan National Health Insurance Research Database (NHIRD) is the good resource to study the clinical effect of Chinese medicine in Taiwan. In our previous proposal, we discovered the use of Astragali radix could improve the clinical survival in prostate cancer through NHIRD. We also discovered that Astragalus polysaccharides (APS), the major compound of Astragali radix, can inhibit the proliferation of PC-3 cells. For mechanism, APS can induce the mitochondrial hyperpolarization of PC-3 cells. APS also inhibited the protein expression of Skp2 and GPX4, the major regulator of ferroptosis, in PC-3 cells. In the immunity, we discovered that APS significantly induced the migratory ability of macrophages. APS also can activate macrophages to secret many cytokines, including TNF-α, the important cytotoxic compound for destroying cancer cells. Moreover, APS can’t induce the PD-L1 expression in PC-3 cells, but APS can inhibit the PD-L1 protein expression induced by IFNγ or oxaliplatin in PC-3 cells. However, the exact role of ferroptosis in prostate cancer under the treatment of APS is still unclear. The effect of APS on the interaction among prostate cancer cells, macrophages and CD8+ T cells is also unclear. We also don’t know the underlying mechanism how APS affect the PD-L1/PD-1 pathway or other pathways in prostate cancer cells and these immune cells. Moreover, the effect and mechanism of combine therapy with APS and anti-prostate cancer drugs or PD-L1/PD-1 inhibitors are also unclear. In this proposal, we will use the different types of prostate cancer cells and these immune cells as our model to evaluate the in vitro effect and mechanism of APS only or in combination with anti-cancer drugs or PD-L1/PD-1 inhibitors in these cells. The interaction and association between PD-L1/PD-1, GPX4, skp2 and other co-factors under the treatment of APS will also be investigated to explore the deeply mechanism. To the end, we will assess the anti-tumor effects of these compounds in animal model. Overall, this proposal will continue the previous proposal,“Merging NHIRD and basic study to create the novel screening platform of anti-prostate cancer herbs”, to discover the potential anti-prostate tumor drugs through the novel screening platform. These compounds could be served as promising anti-prostate cancer therapy for further clinical trial.

Project ID:PC10907-1317
External Project ID:MOST109-2320-B182-021-MY3