Xu Yanming, Li Ying, Yang Xiaodong, Lu Dehua, Zheng Yuanyuan, Tan Jingyun, Li Wenhua, Chen Qi, Liu Yajie, Gao Jing, Wang Shubin
Department of Clinical Medicine, Weifang Medical University Weifang 261031, Shandong, China.
Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center Shenzhen 518036, Guangdong, China.
Am J Cancer Res. 2023 May 15;13(5):1985-1998. eCollection 2023.
Studies have demonstrated that the tumour microenvironment is hypoxia and that hypoxia can induce hypoxia inducible factor-1α (HIF-1α) expression and mediate tumour chemoresistance, which leads to a very poor prognosis for cancer patients. In this study, an economical and practical HIF-1α inhibitor, plasma-activated medium (PAM), was prepared, and its role in colorectal cancer (CRC) was investigated and . We found that HIF-1α expression significantly increased under hypoxia in CRC cells followed by decreased chemosensitivity to oxaliplatin (OXA). Additionally, PAM could reduce HIF-1α expression induced by hypoxia in CRC cells, and compared to PAM or OXA alone, PAM enhanced the chemosensitivity of OXA both in CRC cells and in cell-derived xenografts, as indicated by the inhibition of cell proliferation and tumour growth. Further mechanistic studies revealed that PAM might exert synergistic antitumour activity by inhibiting the MAPK pathway, which deserves further elucidation. In summary, PAM displayed prospective clinical application due to its important function in improving hypoxia in CRC.
研究表明肿瘤微环境处于缺氧状态,且缺氧可诱导缺氧诱导因子-1α(HIF-1α)表达并介导肿瘤化疗耐药,这导致癌症患者预后极差。在本研究中,制备了一种经济实用的HIF-1α抑制剂——等离子体激活培养基(PAM),并研究了其在结直肠癌(CRC)中的作用。我们发现,在缺氧条件下CRC细胞中HIF-1α表达显著增加,随后对奥沙利铂(OXA)的化疗敏感性降低。此外,PAM可降低CRC细胞中缺氧诱导的HIF-1α表达,并且与单独使用PAM或OXA相比,PAM增强了OXA在CRC细胞和细胞衍生异种移植物中的化疗敏感性,这通过抑制细胞增殖和肿瘤生长得以体现。进一步的机制研究表明,PAM可能通过抑制MAPK途径发挥协同抗肿瘤活性,这值得进一步阐明。总之,PAM因其在改善CRC缺氧方面的重要作用而展现出潜在的临床应用前景。