Abstract：
BACKGROUND: The rising incidence of prostate cancer in the U.S. necessitates innovative therapeutic approaches to this disease. Though extensive research has studied Selenium as an anticarcinogen against prostate cancer, results have varied due to overlooked experimental confounds. Recent studies have identified differential effects of various selenium compounds on prostate cancer cells. This study leverages Mixture Design Response Surface Methodology to characterize the ideal combination of select Se forms against the PC-3 prostate cancer cell line.
METHODS: The PC-3 cell line was chosen as a model for its representation of advanced-stage malignancy. Three Se compounds-sodium selenite, methylseleninic acid, and nano-selenium-were selected for their promising antineoplastic potential. Nano-Se particles were synthesized and subsequently characterized by transmission electron microscopy. Cells were cultured, treated with Se compounds, and assessed for viability using an Alamar Blue Assay. IC50 values of individual Se compounds were determined, and treatment combinations evaluated. In collaboration with statical modeling experts, MDRSM was utilized to optimize Se compound combinations.
RESULTS: Absolute IC50 values were identified for methylseleninic acid (5.01 μmol/L), sodium selenite (13.8 μmol/L), and nano-selenium (14.6 μmol/L). Combining methylseleninic acid and sodium selenite resulted in only 5% PC-3 cell viability, whereas individual treatments reduced viability by approximately 45%. Among the tested mixtures, the 50:50 combination of MSA and sodium selenite most effectively decreased PC-3 cell viability. Regression analysis indicated the special cubic model had a strong fit (multiple r² = 0.9853), predicting maximum cell viability reduction from the methylseleninic acid and selenite mixture.
CONCLUSIONS: The specific form of Selenium plays a pivotal role in determining its physiological effects and therapeutic potential against prostate cancer. All three selenium compounds showed variable antineoplastic effects, with a 50:50 mixture of methylseleninic acid and selenite exhibiting optimal results. Nano-selenium, when combined with selenite, showed no additive effect, implying a shared mechanism of action. Our research underscores the critical need to consider Se compound forms as distinct entities in prostate cancer treatment and encourages further exploration of Se compounds against prostate cancer.
METHODS: The PC-3 cell line was chosen as a model for its representation of advanced-stage malignancy. Three Se compounds-sodium selenite, methylseleninic acid, and nano-selenium-were selected for their promising antineoplastic potential. Nano-Se particles were synthesized and subsequently characterized by transmission electron microscopy. Cells were cultured, treated with Se compounds, and assessed for viability using an Alamar Blue Assay. IC50 values of individual Se compounds were determined, and treatment combinations evaluated. In collaboration with statical modeling experts, MDRSM was utilized to optimize Se compound combinations.
RESULTS: Absolute IC50 values were identified for methylseleninic acid (5.01 μmol/L), sodium selenite (13.8 μmol/L), and nano-selenium (14.6 μmol/L). Combining methylseleninic acid and sodium selenite resulted in only 5% PC-3 cell viability, whereas individual treatments reduced viability by approximately 45%. Among the tested mixtures, the 50:50 combination of MSA and sodium selenite most effectively decreased PC-3 cell viability. Regression analysis indicated the special cubic model had a strong fit (multiple r² = 0.9853), predicting maximum cell viability reduction from the methylseleninic acid and selenite mixture.
CONCLUSIONS: The specific form of Selenium plays a pivotal role in determining its physiological effects and therapeutic potential against prostate cancer. All three selenium compounds showed variable antineoplastic effects, with a 50:50 mixture of methylseleninic acid and selenite exhibiting optimal results. Nano-selenium, when combined with selenite, showed no additive effect, implying a shared mechanism of action. Our research underscores the critical need to consider Se compound forms as distinct entities in prostate cancer treatment and encourages further exploration of Se compounds against prostate cancer.
摘要：
背景：在美国，前列腺癌的发病率不断上升，需要对该疾病的创新治疗方法。尽管广泛的研究已经研究了硒作为一种抗前列腺癌的抗癌物质，由于被忽视的实验困惑，结果各不相同。最近的研究已经确定了各种硒化合物对前列腺癌细胞的不同作用。本研究利用混合物设计响应面方法学来表征针对PC-3前列腺癌细胞系的选择Se形式的理想组合。
方法：选择PC-3细胞系作为代表晚期恶性肿瘤的模型。三种硒化合物——亚硒酸钠，甲基硒酸，和纳米硒因其有前途的抗肿瘤潜力而被选择。合成了纳米Se颗粒，随后通过透射电子显微镜进行了表征。培养细胞,用硒化合物处理，并使用AlamarBlue测定法评估生存力。确定了单个Se化合物的IC50值，并评估治疗组合。与静态建模专家合作，MDRSM用于优化Se化合物组合。
结果：确定了甲基硒酸（5.01μmol/L）的绝对IC50值，亚硒酸钠（13.8μmol/L），和纳米硒(14.6μmol/L)。结合甲基硒酸和亚硒酸钠导致只有5％的PC-3细胞活力，而单独的治疗降低了约45%的活力。在测试的混合物中，MSA和亚硒酸钠的50:50组合最有效地降低PC-3细胞活力。回归分析表明，特殊立方模型具有很强的拟合性(倍数r²=0.9853)，预测甲基硒酸和亚硒酸盐混合物的最大细胞活力降低。
结论：硒的特定形式在确定其对前列腺癌的生理作用和治疗潜力方面起着关键作用。所有三种硒化合物都显示出可变的抗肿瘤作用，用50:50的甲基硒酸和亚硒酸盐的混合物表现出最佳效果。纳米硒，当与亚硒酸盐结合时，显示无加性效应，暗示共同的行动机制。我们的研究强调了将Se化合物形式视为前列腺癌治疗中的独特实体的迫切需要，并鼓励进一步探索Se化合物对抗前列腺癌。
方法：选择PC-3细胞系作为代表晚期恶性肿瘤的模型。三种硒化合物——亚硒酸钠，甲基硒酸，和纳米硒因其有前途的抗肿瘤潜力而被选择。合成了纳米Se颗粒，随后通过透射电子显微镜进行了表征。培养细胞,用硒化合物处理，并使用AlamarBlue测定法评估生存力。确定了单个Se化合物的IC50值，并评估治疗组合。与静态建模专家合作，MDRSM用于优化Se化合物组合。
结果：确定了甲基硒酸（5.01μmol/L）的绝对IC50值，亚硒酸钠（13.8μmol/L），和纳米硒(14.6μmol/L)。结合甲基硒酸和亚硒酸钠导致只有5％的PC-3细胞活力，而单独的治疗降低了约45%的活力。在测试的混合物中，MSA和亚硒酸钠的50:50组合最有效地降低PC-3细胞活力。回归分析表明，特殊立方模型具有很强的拟合性(倍数r²=0.9853)，预测甲基硒酸和亚硒酸盐混合物的最大细胞活力降低。
结论：硒的特定形式在确定其对前列腺癌的生理作用和治疗潜力方面起着关键作用。所有三种硒化合物都显示出可变的抗肿瘤作用，用50:50的甲基硒酸和亚硒酸盐的混合物表现出最佳效果。纳米硒，当与亚硒酸盐结合时，显示无加性效应，暗示共同的行动机制。我们的研究强调了将Se化合物形式视为前列腺癌治疗中的独特实体的迫切需要，并鼓励进一步探索Se化合物对抗前列腺癌。
