利用Postbiotics促进化疗:N-乙酰半胱氨酸和四氢β-卡波林羧酸作为胰腺癌和结直肠癌癌症的增效剂
Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro β-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer.
Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro β-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer.
癌症(PC)和癌症(CRC)是最致命的恶性肿瘤之一,越来越多的证据表明肠道微生物群在其进展中的作用。本研究旨在探索两种微生物群衍生的抗生素N-乙酰半胱氨酸(NAC)和四氢β-卡布林羧酸(THC)在靶向PC和CRC的一些标志性特征方面的抗癌潜力,无论是作为独立药物还是与标准化疗药物(用于PC的吉西他滨和用于CRC的5-氟尿嘧啶(5-FU))联合使用。细胞活力测定和IC50测定使用Muse™计数和活力试剂盒或磺基罗丹明B测定法进行评估;通过Annexin V/碘化丙啶测定细胞死亡,并通过流式细胞术分析碘化丙啶评估的细胞周期。在这里,我们发现NAC选择性地降低了PC细胞BxPC-3的存活率,而不会引发凋亡,同时有效地诱导了PC细胞Panc-1和CRC细胞系的凋亡。THC在所有测试的PC和CRC细胞中表现出更强的抗癌活性,抑制增殖并促进凋亡,即使在较低浓度下也是如此。联合治疗产生了有希望的增强效果。NAC通过增加细胞凋亡增强吉西他滨对Panc-1细胞的细胞毒性。NAC与5-FU联合使用时,也会增加CRC细胞的凋亡。THC通过增加凋亡和诱导BxPC-3细胞周期变化,进一步增强了吉西他滨对Panc-1细胞的影响。在CRC模型中,THC与5-FU的联合治疗降低了所有细胞的存活率并增加了细胞凋亡。这些发现提供了初步的体外证据,支持在PC和CRC中将微生物群衍生的抗生素与常规化疗相结合的潜力。
Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota's role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro β-carboline carboxylic acid (THC), in targeting some hallmark traits of PC and CRC, both as standalone agents and in combination with standard chemotherapeutics (gemcitabine for PC and 5-fluorouracil (5-FU) for CRC). Cell viability assays and IC determination was assessed using either the Muse™ Count & Viability Kit or the Sulforhodamine B assay; cell death was determined by Annexin V/Propidium Iodide and cell cycle assessed by Propidium Iodide was analyzed by flow cytometry. Here, we found that NAC selectively reduced the viability of PC cells BxPC-3 without triggering apoptosis, while effectively inducing apoptosis in PC cells Panc-1 and in CRC cell lines. THC exhibited stronger anticancer activity, inhibiting proliferation and promoting apoptosis in all tested PC and CRC cells, even at lower concentrations. Combination treatments yielded promising enhancement effects. NAC enhanced the cytotoxicity of gemcitabine in Panc-1 cells through increased apoptosis. NAC, when combined with 5-FU, also increased apoptosis of CRC cells. THC further potentiated gemcitabine's impact on Panc-1 cells by increasing apoptosis and by inducing cell cycle changes in BxPC-3. In the CRC model, THC co-treatment with 5-FU reduced cell viability and increased apoptosis in all cells. These findings provide preliminary in vitro evidence supporting the potential of integrating microbiota-derived postbiotics with conventional chemotherapy both in PC and CRC.
Vanessa Rodriguez, Annacandida Villani, Margarida Sénica, Concetta Panebianco, Valerio Pazienza, Ana Preto. Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro β-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer.. Cancers. 2026; doi:10.3390/cancers18030369.
Vanessa Rodriguez, Annacandida Villani, Margarida Sénica, Concetta Panebianco, Valerio Pazienza, Ana Preto (2026). Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro β-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer.. Cancers. https://doi.org/10.3390/cancers18030369
Vanessa Rodriguez, Annacandida Villani, Margarida Sénica, Concetta Panebianco, Valerio Pazienza, Ana Preto. Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro β-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer.[J]. Cancers, 2026 doi:10.3390/cancers18030369.
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