Grigoryan Rita, Keshelava Nino, Anderson Clarke, Reynolds C Patrick
Developmental Therapeutics Section, Children's Hospital of Los Angeles, Los Angeles, CA, USA.
Methods Mol Med. 2005;110:87-100. doi: 10.1385/1-59259-869-2:087.
Highly aggressive, rapidly growing tumors are often hypoxic, owing to an inadequate supply relative to consumption of oxygen (O2) in the expanding tumor mass, or growth in tissues with physiologically low O2 concentrations (such as bone marrow). Selection of tumor cells that can grow or survive under hypoxic conditions appears from both experimental and clinical studies to impact tumor progression, response to therapy, and to increase resistance to radiation and to certain cytotoxic drugs. Therefore, the predictive value of preclinical testing of anticancer agents in cell culture might be improved by conducting testing in conditions of physiological hypoxia. We review the impact of hypoxia on anticancer drug cytotoxicity and the methods used in our laboratory to asses the cytotoxic activity of single antineoplastic drugs under conditions of physiological hypoxia.
高度侵袭性、快速生长的肿瘤通常处于缺氧状态，这是由于在不断扩大的肿瘤块中，相对于氧气（O2）的消耗，供应不足，或者在生理氧浓度较低的组织（如骨髓）中生长。实验和临床研究均表明，选择能在缺氧条件下生长或存活的肿瘤细胞会影响肿瘤进展、对治疗的反应，并增加对辐射和某些细胞毒性药物的抗性。因此，通过在生理缺氧条件下进行测试，可能会提高细胞培养中抗癌药物临床前测试的预测价值。我们综述了缺氧对抗癌药物细胞毒性的影响，以及我们实验室在生理缺氧条件下评估单一抗肿瘤药物细胞毒性活性所使用的方法。
