RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The potential role of cannabidiol (CBD) in lung cancer therapy: a systematic review of preclinical and clinical evidence.
The potential role of cannabidiol (CBD) in lung cancer therapy: a systematic review of preclinical and clinical evidence.
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CBD 作为肺癌治疗的辅助手段具有前景,可针对肿瘤生长、转移和治疗耐药等关键癌症特征。
肺癌是全球发病率和致死率最高的癌症之一,晚期治疗选择有限。大麻素近来作为潜在抗癌药物受到关注,其中来源于大麻、无精神活性的大麻二酚(CBD)是最有前景的候选物。与Δ9-四氢大麻酚(THC)不同,CBD不具有精神活性,通常耐受性良好且安全性特征较佳。此外,CBD可影响凋亡、上皮-间质转化(EMT)和免疫调节等多种与癌症相关的通路,这些过程对非小细胞肺癌(NSCLC)尤为重要,因此有充分理由重点研究CBD用于肺癌治疗的潜力。
研究者在PubMed、Scopus、Web of Science和Google Scholar开展系统检索,使用“CBD”“肺癌”和“非小细胞肺癌”等预设关键词。依据PRISMA指南筛选2007至2025年的研究,最终纳入19项。
纳入研究包括13项体外研究、4项动物体内研究和2篇临床报告。各研究中,细胞实验所用CBD浓度为低微摩尔水平(1–10 μM),人体病例口服剂量为每日200–600 mg。机制方面,CBD可通过激活PPAR、线粒体功能障碍和氧化应激等途径诱导凋亡;抑制EMT、下调侵袭性标志物,并通过增强CD8+ T细胞和NK细胞活性调节肿瘤微环境。此外,CBD可提高药物摄取并克服耐药,从而与顺铂、放疗等常规疗法产生协同作用。
CBD有望作为肺癌治疗的辅助药物,作用于肿瘤生长、转移和治疗耐药等关键癌症特征。尽管临床前证据较充分,临床试验仍有限。未来研究应重点优化给药方案、评估长期安全性,并在大规模人体研究中验证现有发现。
Lung cancer is one of the most prevalent and lethal cancers worldwide, with limited therapeutic options in advanced stages. Cannabinoids have recently attracted attention as potential anticancer agents; however, cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has emerged as the most promising candidate. Unlike 9-tetrahydrocannabinol (THC), CBD lacks psychoactive properties, is generally well tolerated, and demonstrates a favorable safety profile. Moreover, CBD influences multiple cancer-relevant pathways-including apoptosis, epithelial-to-mesenchymal transition (EMT), and immune modulation-that are particularly relevant to non-small cell lung cancer (NSCLC). These features provide a strong rationale for focusing on CBD in lung cancer therapy.
A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar, using defined keywords such as "CBD," "lung cancer," and "non-small cell lung cancer." Studies from 2007 to 2025 were screened following PRISMA guidelines, and 19 studies met the inclusion criteria.
Nineteen studies met the inclusion criteria, comprising 13 in vitro studies, 4 in vivo animal studies, and 2 clinical reports. Across these studies, CBD was administered at concentrations ranging from low micromolar levels (1-10 M) in cell-based experiments to oral doses of 200-600 mg/day in human cases. Mechanistically, CBD induced apoptosis through pathways such as PPAR- activation, mitochondrial dysfunction, and oxidative stress. It inhibited epithelial-to-mesenchymal transition (EMT), downregulated invasive markers, and modulated the tumor microenvironment by enhancing CD8 + T cell and NK cell activity. Furthermore, CBD showed synergistic effects with conventional therapies (e.g., cisplatin, radiotherapy) by increasing drug uptake and overcoming resistance.
CBD holds promise as an adjunct in lung cancer therapy, addressing key cancer hallmarks such as tumor growth, metastasis, and treatment resistance. While preclinical evidence is robust, clinical trials remain limited. Future research should focus on optimizing dosing regimens, evaluating long-term safety, and validating these findings in large-scale human studies.
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