| Background:Prostate cancer is one of the most common cancers in men all over the world.According to the statistics published in CA cancer J Clin in 2021,there are about 1414000 new cases of prostate cancer and375000 deaths worldwide.Meanwhile,the incidence rate of prostate cancer is increasing in many countries.In recent years,the mortality rate in developed countries has decreased,while the mortality rate in developing countries is increasing significantly.For prostate cancer,the existing treatment methods mainly include observation treatment,surgical treatment,radiotherapy,endocrine therapy,chemotherapy and so on.For early localized tumors,observation and surgery are generally used.The main surgical methods include:(1)open retropubic prostatectomy(RRP);(2)Laparoscopic radical prostatectomy;(3)Robot assisted laparoscopic prostatectomy(RALP).Hormone independent prostate cancer is treated with endocrine drugs such as adrenocortical hormone and estrogen,while hormone resistant prostate cancer is better treated with chemotherapy drugs such as vincristine.However,the prognosis of these nonspecific treatments is not optimistic.Androgen independent growth and distant metastasis of cancer cells are two major obstacles affecting the clinical treatment effect of prostate cancer.Therefore,the development of more effective targeted drugs has become a major research focus and difficulty in the clinical treatment of prostate cancer.Tumor nanotechnology is a new technology.It has great potential in tumor targeted therapy and molecular application of chemotherapy.Nano drug delivery system has been proved to improve the cell targeting of anticancer drugs.Specific nanodrugs can also show radiosensitization.At present,a large number of preclinical and clinical studies have been carried out in the world to explore the effect and toxic and side effects of nanoparticles carrying drugs against tumors.At present,nanoparticles with in-depth anti-tumor research include nano selenium particles,nano zinc particles,nano silica particles and nano gold / silver particles.Nano gold/silver particles(AuNPs / AgNPs)have good biocompatibility,easy synthesis,good monodispersity and adjustable surface functionality.In particular,the synthesis of AuNPs can be easily controlled to obtain nanoparticles of different sizes.In addition,AuNPs were found to have good targeting and biological activity against tumors in vivo and in vitro.Therefore,the development of new antitumor drugs based on AuNPs has become a new hot research field of tumor nanotechnology.AuNPs has potent anti-tumor activity against many kinds of tumor cells,such as ovarian cancer,breast cancer,liver cancer and lung cancer.This activity has been verified in mice,rats and other animals.Molecular mechanism studies show that AuNPs may play an anti-tumor role by regulating a variety of tumor related signal pathways.AuNPs are also often used as a delivery system to combine with therapeutic molecules(protein antibodies or micro RNA)to exert a strong inhibitory effect on cancer cells.In addition,AuNPs have specific and unique physical,chemical,optical and electronic properties,which makes researchers speculate that AuNPs can be used as radiotherapy sensitizers for a long time.Although the research on some mechanisms explains the principle of the radiosensitization characteristics of AuNPs from the physical,chemical and biological perspectives,there are still some areas that are not clear.This research paper is divided into two parts: the first part: the synthesis,identification and anti prostate cancer mechanism of nano gold: This is the key content of this paper.Part II: Study on the radiosensitization effect of nano gold on prostate cancer cells: This is based on the continuation and expansion of the first part.Method1.AuNPs were prepared by trisodium citrate reduction method,and senps were characterized and identified by UV-Vis absorption spectroscopy;The size and shape of AuNPs were measured by transmission electron microscope;The elemental composition of synthetic particles was determined by energy spectrometer to determine the purity and characterization of synthetic products;2.Prostate cancer cell lines and primary cultured cells were treated with synthetic AuNPs,and the antitumor activity of AuNPs was determined by MTT assay;3.The differentially secreted proteins of AuNPs treated and untreated prostate cancer cells were identified by secretory proteomics;4.Prostate cancer cells were treated with X-ray(IR)and AuNPs to determine their synergistic effect;5.q RT-PCR,Western blotting and ELISA were used to verify the differential expression of key molecules between groups;The key molecules regulated by AuNPs were found;6.The antitumor activity of NPs xenografts in nude mice was verified.ResultsPart ?: synthesis,identification and anti prostate cancer mechanism of AuNPs: In this study,AuNPs were synthesized;the average size of the particles was 62.2 ± 6 nm with smooth surface and multiple shapes,which were determined using transmission electron microscopy and field emission scanning electron microscopy.The selected area electron diffraction patterns suggested that the synthesized AuNPs were crystalline.The XPS spectrum of the synthesized AuNPs has presented an intense peak at 100 e V,signifying the entire composition of Au in the developed AuNPs.This synthesized AuNPs showed the most potent efficacy in prostate cancer cells,regardless of whether or not they were androgen-dependent.Secretome determinations using twodimensional difference in-gel electrophoresis(2D-DIGE),followed by enzyme-linked immunosorbent assay and quantitative reverse transcriptase-polymerase chain reaction validations,have identified a series of secretory proteins that were dysregulated by AuNPs treatment in prostate cancer cells,many of which are highly involved in cytokine–chemokine functions,including CXCL3,interleukin-10,CCL2,and matrix metalloproteinase 9(MMP9).Further research on molecular mechanism has indicated that AuNPs can trigger the secretion of anticancer factors and myeloid cell-polarizing factors from tumor cells through MMP9 inhibition.Part ?: Study on the radiosensitization effect of AuNPs on prostate cancer cells:In this part,it was found that the combined use of AuNPs and IR could enhance its antitumor activity against prostate cancer cells and inhibit malignant indexes such as tumor migration and invasion;AuNPs can inhibit TRAF6 / NF-? B pathway to inhibit IR induced CCL2 production,which may be the main reason for the synergistic effect of AuNPs and IR.In addition,AuNPs can re sensitize radioresistant prostate cancer cells by limiting the production of CCL2.ConclusionAuNPs synthesized in this study exert antitumor activity on prostate cancer cells by regulating the secretion of inflammatory factors such as MMP9 and CCL2,regulating a variety of cancer cell related functions,including regulating tumor cell proliferation,migration and invasion,regulating the information interaction between tumor cells and immune microenvironment,regulating the IR sensitivity of tumor cells,etc.These findings clearly show the potential of AuNPs in the treatment of prostate cancer and may provide a new direction for the treatment of prostate cancer in the future. |
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