Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.
Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing, Jiangsu, 210023, P.R. China.
Curr Mol Pharmacol. 2022;15(3):487-501. doi: 10.2174/1874467214666210811145752.
Hypoxia, a common feature of malignant tumours, is mainly caused by insufficient oxygen supply. Hypoxia is closely associated with cancer development, affecting cancer invasion, metastasis, energy metabolism, and other pathological processes, and is not conducive to cancer treatment and prognosis. Tumour cells exacerbate metabolic abnormalities to adapt to the hypoxic microenvironment, especially to enhance aerobic glycolysis. Glycolysis leads to an acidic microenvironment in cancer tissues, enhancing cancer metastasis, deterioration, and drug resistance. Therefore, hypoxia is a therapeutic target that cannot be ignored in cancer treatment. The adaptation of tumour cells to hypoxia is mainly regulated by hypoxia-inducible factors (HIFs), and the stability of HIFs is improved under hypoxic conditions. HIFs can promote glycolysis in tumours by regulating glycolytic enzymes, transporters, and the TCA cycle. In addition, HIFs indirectly affect glycolysis by interacting with non- coding RNAs. Therefore, targeting hypoxia and HIFs is important for tumour therapy.
缺氧是恶性肿瘤的常见特征，主要由供氧不足引起。缺氧与癌症的发展密切相关，影响癌症的侵袭、转移、能量代谢等病理过程，不利于癌症的治疗和预后。肿瘤细胞加剧代谢异常以适应缺氧微环境，特别是增强有氧糖酵解。糖酵解导致癌症组织的酸性微环境，增强癌症转移、恶化和耐药性。因此，缺氧是癌症治疗中不可忽视的治疗靶点。肿瘤细胞对缺氧的适应主要受缺氧诱导因子（HIFs）调节，HIFs 在缺氧条件下稳定性提高。HIFs 通过调节糖酵解酶、转运体和 TCA 循环来促进肿瘤中的糖酵解。此外，HIFs 通过与非编码 RNA 相互作用间接影响糖酵解。因此，针对缺氧和 HIFs 是肿瘤治疗的重要手段。
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