肿瘤细胞治疗研究
英文原题：Cytotoxic and Immunomodulatory Effects of Phormidesmis molle Extract on Human Cells In Vitro.
在72小时，用最高浓度（200 µg/mL）处理使Caco-2细胞活力降至74%，HT-29细胞降至69-70%，LS-180细胞降至59-61%。
Phormidesmis属蓝细菌被认为是具有抗癌和免疫调节特性的生物活性次级代谢产物的有前景来源。在本研究中，我们研究了从Phormidesmis molle PACC（Plovdiv藻类培养物保藏中心）8140获得的提取物的细胞毒性和免疫学效应及其化学成分。该提取物通过LC-ESI-MS/MS（液相色谱-电喷雾电离-串联质谱）进行了分析，并对选定化合物进行了in silico ADMET（吸收、分布、代谢、排泄和毒性）建模评估。该提取物的细胞毒性潜力通过MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）试验在体外对人结直肠腺癌细胞系（Caco-2、HT-29和LS-180）进行了评估。该提取物的免疫学影响在从健康供者分离的人外周血单核细胞（PBMCs）上进行了评估。PBMCs用100 µg/mL提取物处理48 h，随后进行流式细胞术免疫表型分析和基于ELISA（酶联免疫吸附试验）的细胞因子定量。该提取物在暴露24、48和72 h后诱导了癌细胞活力的浓度和时间依赖性下降。在72 h时，用最高浓度（200 µg/mL）处理使Caco-2细胞活力降至74%，HT-29细胞降至69-70%，LS-180细胞降至59-61%。用Phormidesmis提取物处理后观察到的形态学变化显示，在受试结直肠癌细胞系中具有明显的细胞毒性和凋亡相关效应。免疫表型分析显示自然杀伤（NK）细胞（CD56+和/或CD16+）显著扩增。CD3-CD56-CD16+ NK群体显著增加（从67.7 ± 0.未处理PBMC中为95%，而提取物处理后的PBMC中为94.66 ± 0.90%，p < 0.001）。相反，CD8 + T细胞、CD19 + B细胞和CD11b + 单核细胞的比例显著降低（分别从21.5 ± 4.50%降至7.22 ± 0.41%，从11.9 ± 1.70%降至6.06 ± 0.42%，从66.4 ± 0.60%降至34.4 ± 0.87%）。细胞因子分析显示Th1相关细胞因子受到强烈抑制，干扰素γ（IFN-γ，对照组为461 ng/mL，提取物处理培养物为84 ng/mL）和肿瘤坏死因子α（TNF-α）水平显著降低（对照组为169 ng/mL，提取物处理培养物为32 ng/mL），而白细胞介素-6（IL-6）中度升高（从对照组158 ng/mL升至提取物处理培养物的234 ng/mL），IL-10仍保持低水平。这些发现表明，P. molle提取物兼具对癌细胞的细胞毒活性和强效免疫调节作用，凸显其作为基于免疫的治疗策略中生物活性化合物来源的潜力。
Cyanobacteria of the genus Phormidesmis are recognized as a promising source of biologically active secondary metabolites with anticancer and immunomodulatory properties. In the present study, we investigated both the cytotoxic and immunological effects of an extract obtained from Phormidesmis molle PACC (Plovdiv Algal Culture Collection) 8140 as well as its chemical composition. The extract was profiled by LC-ESI-MS/MS (Liquid chromatography-electrospray ionization-tandem mass spectrometry), and selected compounds were evaluated with in silico ADMET (Absorption, distribution, metabolism, excretion and toxicity) modeling. The cytotoxic potential of the extract was evaluated in vitro using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay on human colorectal adenocarcinoma cell lines (Caco-2, HT-29, and LS-180). The immunological impact of the extract was assessed on human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. PBMCs were treated with 100 µg/mL extract for 48 h, followed by flow cytometric immunophenotyping and ELISA (Enzyme-linked immunosorbent assay)-based cytokine quantification. The extract induced a concentration- and time-dependent decrease in cancer cell viability after 24, 48, and 72 h of exposure. At 72 h, treatment with the highest concentration (200 µg/mL) reduced cell viability to 74% in Caco-2 cells, 69-70% in HT-29 cells, and 59-61% in LS-180 cells. Morphological changes observed after treatment with Phormidesmis extract showed pronounced cytotoxic and apoptosis-related effects in the colorectal cancer cell lines tested. Immunophenotyping revealed a pronounced expansion of natural killer (NK) cells (CD56 + and/or CD16 + ). CD3 - CD56 - CD16 + NK population was markedly increased (from 67.7 ± 0.95% in non-treated PBMCs to 94.66 ± 0.90% in extract-treated PBMCs, p < 0.001). In contrast, the proportions of CD8 + T cells, CD19 + B cells, and CD11b + monocytes were significantly reduced (from 21.5 ± 4.50% to 7.22 ± 0.41%, from 11.9 ± 1.70% to 6.06 ± 0.42%, and from 66.4 ± 0.60% to 34.4 ± 0.87%, respectively). Cytokine analysis demonstrated strong suppression of Th1-associated cytokines, with significantly reduced interferon gamma (IFN-γ, 461 ng/mL in controls vs. 84 ng/mL in extract-treated cultures) and tumor necrosis factor alpha (TNF-α) levels (169 ng/mL in controls vs. 32 ng/mL in extract-treated cultures), whereas nterleukin-6 (IL-6) was moderately elevated (from 158 ng/mL in controls to 234 ng/mL in extract-treated cultures) and IL-10 remained low. These findings demonstrate that P. molle extract combines cytotoxic activity against cancer cells with potent immunomodulatory effects, highlighting its potential as a source of bioactive compounds for immune-based therapeutic strategies.
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