Martviset Pongsakorn, Chantree Pathanin, Tongsiri Nisit, Plengsuriyakarn Tullayakorn, Na-Bangchang Kesara
Division of Parasitology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.
Graduate Program in Applied Biosciences, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.
PLoS One. 2025 May 13;20(5):e0323732. doi: 10.1371/journal.pone.0323732. eCollection 2025.
Cholangiocarcinoma (CCA) is one of the most aggressive cancers with a poor prognosis. Current treatment strategies involve hepatobiliary surgery, chemotherapy, radiotherapy, and supportive care; however, the success of these treatments remains limited. Therefore, this study investigated the potential of Atractylodes lancea (Thunb) D.C. (AL) in limiting the progress of CCA by targeting the expression of cancer-related genes involved in immune responses and circulating tumor cells. The study was part of Phase 2A clinical trial in advanced-stage intrahepatic iCCA (iCCA) patients: Group 1 (n = 16) received low-dose AL (capsule formulation of the standardized extract of AL: CMC-AL) with standard supportive care, Group 2 (n = 16) received high-dose AL with standard supportive care, and Group 3 (n = 16) received standard supportive care alone. Venous whole blood samples (EDTA, 5 ml) were collected from each patient on Day 1 and Day 90 and the non-CCA subjects (n = 16) on Day 1. Fifty-nine samples (48 and 11 samples for Day 1 and Day 90, respectively) were processed for total RNA isolation. Gene expression was evaluated using reverse transcription followed by a PCR array. Regardless of dosage, gene expression patterns in the AL-treated groups closely resembled those of the healthy subjects. Specifically, cancer-associated genes, including VEGF-A, NR4A3, Ki-67, and EpCAM, were significantly down-regulated. Additionally, the expression levels of immune-related genes were modulated in AL-treated patients. The treatment groups exhibited lower levels of the pro-inflammatory cytokine IL-6, increased expression of the anti-inflammatory cytokine IL-10, and cell-mediated immune-related molecules such as CTLA4 and PFR1. These findings suggest the potential of AL for iCCA treatment. However, additional studies are required to confirm the correlation between gene and protein expression profiles, as well as CTCs profile.
胆管癌（CCA）是侵袭性最强的癌症之一，预后较差。目前的治疗策略包括肝胆手术、化疗、放疗和支持治疗；然而，这些治疗的成功率仍然有限。因此，本研究通过靶向参与免疫反应和循环肿瘤细胞的癌症相关基因的表达，研究了白术（AL）在限制CCA进展方面的潜力。该研究是晚期肝内iCCA患者2A期临床试验的一部分：第1组（n = 16）接受低剂量AL（AL标准化提取物的胶囊制剂：CMC-AL）并辅以标准支持治疗，第2组（n = 16）接受高剂量AL并辅以标准支持治疗，第3组（n = 16）仅接受标准支持治疗。在第1天和第90天从每位患者采集静脉全血样本（EDTA，5 ml），并在第1天从非CCA受试者（n = 16）采集样本。对59个样本（第1天和第90天分别为48个和11个样本）进行总RNA分离。使用逆转录随后进行PCR阵列评估基因表达。无论剂量如何，AL治疗组的基因表达模式与健康受试者的非常相似。具体而言，包括VEGF-A、NR4A3、Ki-67和EpCAM在内的癌症相关基因显著下调。此外，AL治疗患者中免疫相关基因的表达水平得到调节。治疗组促炎细胞因子IL-6水平较低，抗炎细胞因子IL-10表达增加，以及细胞介导免疫相关分子如CTLA4和PFR1表达增加。这些发现表明AL在iCCA治疗方面具有潜力。然而，需要进一步研究以证实基因和蛋白质表达谱以及循环肿瘤细胞谱之间的相关性。
