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Synergistic effect and mechanism study of Phycocyanin photosensitizer combined with Selenium against lung tumor in mouse

ABSTRACT: We used selenium as a photodynamic anti-tumor synergist of phycocyanin to explore its inhibitory effect on lung cancer and its molecular mechanism in vitro. First of all, we used LLC-luc mouse lung cancer cells to establish a tumor-bearing model. Selenium-enriched phycocyanin was injected next to the tumor. When it was absorbed by the tumor tissue, the tumor site was irradiated by a 620nm wavelength laser. The changes in tumor size were monitored in real-time and the physiological indexes of mice were measured. It was found that selenium phycocyanin photodynamic therapy could enhance the inhibitory effect of tumors and improve the level of antioxidation in tumor-bearing mice. In addition, the pathological section observation and electron microscope microstructure analysis of the tumor tissue showed that the effect of the selenium-enriched phycocyanin photodynamic treatment group was more significant. At the same time, the tumor tissue transcriptional group sequencing analysis and qRT-PCR verification analysis showed that selenium-enriched phycocyanin photodynamic treatment group could reduce the expression of Mmp13, Serpine1, Vegfa, and Ppbp genes inhibit tumor cell metastasis and proliferation, up-regulate the expression of Ccl2, Ccl3, Cxcl2 and down-regulate the expression of Ccl24 chemokine, and promote tumor local immunity. Our results show that selenium phycocyanin photodynamic therapy plays an anti-tumor effect by promoting tumor cell apoptosis, reducing inflammation, and promoting tumor immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE192635 | GEO | 2023/01/01

REPOSITORIES: GEO

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Project description:Background & aim: Micronutrient deficiencies, particularly those of zinc and selenium, are common in persons living with human immunodeficiency virus (PLWHIV), and have been associated with the development of non-AIDS related comorbidities, impaired immune system function, HIV disease progression and mortality. The implementation of intervention strategies on clinically stable long-term-treated PLWHIV could bring potential benefits on impeding or delaying the onset of non-AIDS associated comorbidities, improving their health status and overall quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density (BMD), lipids profile, glucose and immune system activation and function on PLWHIV on antiretroviral therapy (ART) without metabolic diseases. Methods: This pilot trial was composed of 60 PLWHIV on ART who were randomly assigned to either zinc, selenium, zinc + selenium supplementation or to a control group. Daily supplementation was prescribed during 6 months as follows: the zinc group received 30 mg of zinc gluconate, the selenium group received 200 mcg of selenium yeast and the zinc + selenium group received both micronutrients at the same doses and presentations. Individuals in the control group were followed during the same time without any nutritional supplementation. Body composition (weight, body mass index [BMI], fat mass and muscle mass), BMD, blood pressure, blood biochemical parameters (cholesterol, glucose and triglycerides), serum zinc and selenium concentrations, CD4+ T cell count and CD4+ and CD8+ T cells immune activation were assessed before and after supplementation. One individual of each supplementation group and one of the control group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p=0.03), fat mass in kg (p=0.03) and percentage (p=0.02), as well as trunk fat (p=0.01), were significantly decreased after selenium supplementation. No changes were observed for body composition, BMD, biochemical determinations or blood pressure on the other intervention groups after supplementation (p>0.05 in all cases). The CD4+ T cells frequency and count significantly increased after selenium and zinc supplementation (p=0.03, p=0.05 respectively). CD4+ and CD8+ T-cell immune activation did not change after supplementation (p>0.05 in both cases). On the single cell transcriptome analysis, zinc and selenium supplementation significantly change de expression of genes associated with the function of naive and memory CD8+ T cells (adjusted p<0.05 in all cases). Conclusions: Selenium supplementation have beneficial effects on the body composition, while zinc and selenium supplementation increased CD4+ T cell replenishment of PLWHIV on long-term ART without metabolic diseases. Additionally, zinc and selenium supplementation modified the expression of genes associated with the function of naive and memory CD8+ T cells. Zinc and selenium supplementation are a simple, low-cost, and safe nutritional treatment that represents a complementary intervention to improve the health status and increase the quality of life of clinically stable PLWHIV without metabolic diseases. Registered: Under ClinicalTrails.gov identifier NCT03421314

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Synergistic effect and mechanism study of Phycocyanin photosensitizer combined with Selenium against lung tumor in mouse

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