Meenu Meenakshi, Verma Vipin Kumar, Seth Amlesh, Sahoo Ranjit Kumar, Gupta Pooja, Arya Dharamvir Singh
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Department of Urology, All India Institute of Medical Sciences, New Delhi, India.
Curr Ther Res Clin Exp. 2020 Oct 28;93:100610. doi: 10.1016/j.curtheres.2020.100610. eCollection 2020.
Metastatic burden and aggressive behavior determine severity stratification and guide treatment decisions in prostate cancer (PCa). Monoamine oxidase A (MAOA) may promote tumor burden and drug/castration resistance in PCa. A positive association will pave the way for MAOA inhibitors such as moclobemide for PCa therapy.
To analyze MAOA in peripheral blood mononuclear cells qualitatively and p38, c-Jun N-terminal kinases, nuclear factor kappa B, and their phosphorylated forms, vascular endothelial growth factor (angiogenesis), transforming growth factor beta, interleukin 6, and tumor necrosis factor-α (cytokines), Bcl-2 associated X, B-cell lymphoma 2, and P53 (apoptosis), prostate-specific membrane antigen, and epithelial cell adhesion molecules (surface markers) in plasma of patients with PCa.
This was a 1-year pilot study in which patients with PCa were recruited and stratified into 2 groups and subgroups: treatment-naive with (M1) (n = 23) or without (M0) (n = 23) bone metastasis; hormone-sensitive prostate cancer (n = 26) or hormone/castration-resistant prostate cancer (n = 26). MAOA was detected using ELISA and other proteins were detected using immunoblotting technique.
MAOA was detected in 8.6% of M0 compared with 30.4% of M1 patients, and in 7.7% of hormone-sensitive compared with 27% of hormone/castration resistant PCa patients, associating it with bone metastasis and castration resistance. Multivariable regression analysis showed a correlation of MAOA with serum prostate-specific antigen, a marker for progression in PCa (Pearson correlation coefficient = 0.30; < 0.01). In patients with positive MAOA, there was overexpression of p38, phosphorylated-p38, c-Jun N-terminal kinases, phosphorylated c-Jun N-terminal kinases, nuclear factor kappa B, phosphorylated nuclear factor kappa B, transforming growth factor beta, vascular endothelial growth factor, interleukin 6, tumor necrosis factor α, Bcl-2 associated X, B-cell lymphoma 2, prostate-specific membrane antigen, and epithelial cell adhesion molecule in M1 compared with M0 group patients, associating these proteins with tumor burden. Overexpression of Bcl-2 associated X, tumor protein 53, c-Jun N-terminal kinases, nuclear factor kappa B, transforming growth factor beta, vascular endothelial growth factor, and prostate-specific membrane antigen and underexpression of B-cell lymphoma 2 and phosphorylated nuclear factor kappa B were observed in hormone-sensitive prostate cancer compared with hormone/castration-resistant prostate cancer, associating these proteins with castration resistance.
Association of key molecules of oncogenesis and metastasis with MAOA suggests that MAOA inhibitors such as moclobemide might be effective in the management of PCa.
转移负担和侵袭性行为决定前列腺癌（PCa）的严重程度分层并指导治疗决策。单胺氧化酶A（MAOA）可能促进PCa的肿瘤负担及耐药/去势抵抗。MAOA与PCa的正相关关系将为如吗氯贝胺等MAOA抑制剂用于PCa治疗铺平道路。
分析PCa患者外周血单核细胞中的MAOA，以及血浆中p38、c-Jun氨基末端激酶、核因子κB及其磷酸化形式、血管内皮生长因子（血管生成）、转化生长因子β、白细胞介素6和肿瘤坏死因子-α（细胞因子）、Bcl-2相关X蛋白、B细胞淋巴瘤2蛋白和P53（细胞凋亡）、前列腺特异性膜抗原和上皮细胞粘附分子（表面标志物）。
这是一项为期1年的前瞻性研究，招募PCa患者并将其分为2组及亚组：初治有（M1）（n = 23）或无（M0）（n = 23）骨转移；激素敏感性前列腺癌（n = 26）或激素/去势抵抗性前列腺癌（n = 26）。采用酶联免疫吸附测定法检测MAOA，采用免疫印迹技术检测其他蛋白。
M0患者中8.6%检测到MAOA，而M1患者中为30.4%；激素敏感性PCa患者中7.7%检测到MAOA，而激素/去势抵抗性PCa患者中为27%，提示MAOA与骨转移和去势抵抗相关。多变量回归分析显示MAOA与血清前列腺特异性抗原相关，前列腺特异性抗原是PCa进展的标志物（Pearson相关系数 = 0.30；<0.01）。MAOA阳性患者中，与M0组患者相比，M1组患者的p38、磷酸化p38、c-Jun氨基末端激酶、磷酸化c-Jun氨基末端激酶、核因子κB、磷酸化核因子κB、转化生长因子β、血管内皮生长因子、白细胞介素6、肿瘤坏死因子α、Bcl-2相关X蛋白、B细胞淋巴瘤2蛋白、前列腺特异性膜抗原和上皮细胞粘附分子均有过表达，提示这些蛋白与肿瘤负担相关。与激素/去势抵抗性前列腺癌相比，激素敏感性前列腺癌中观察到Bcl-2相关X蛋白、肿瘤蛋白53、c-Jun氨基末端激酶、核因子κB、转化生长因子β、血管内皮生长因子和前列腺特异性膜抗原过表达，以及B细胞淋巴瘤2蛋白和磷酸化核因子κB低表达，提示这些蛋白与去势抵抗相关。
肿瘤发生和转移的关键分子与MAOA相关，提示吗氯贝胺等MAOA抑制剂可能对PCa治疗有效。
