甲磺酸伊马替尼对乏氧hela细胞放射敏感性影响的分析-effect of imatinib mesylate on radiosensitivity of hypoxic hela cells.docxVIP

drugs;Low does of imatinib mesylate(0.1μmol/L)had a positive effect on the radiosensitivity of Hela under both normal and hypoxia growth conditions(P ＜0.05),and compared with paclitaxel,the radiation sensitizing effect has no significant difference(P＞0.05);Hypoxic could induce PDGFR-β phosphorylation as well asenhance the expression of VEGF,imatinib mesylate could block the expression of PDGFR-βphosphorylation and inhibition the enhanced expression of VEGF on Hela under hypoxic conditions in vitro.Conclusion:Imatinib mesylate have radiation sensitizing effect on Hela under different growth conditions,and it may be used as a radiation sensitizer for the next phase of research;Imatinib mesylate could kill hypoxic cells by inhibit p-PDGFR-β and/or VEGF and reduced radiotherapy resistance of hypoxic cells;this contribution give us a clue that the PDGF / VEGF pathway may be one of the targets of imatinib mesylate’s sensitization,providng a novel way for reduce the radiation resistance of tumor;In the early state of hypoxic,cells are in an instability condition and more easlier to be killed,once they enters into a stable state then they could behave resistance to chemotherapy and radiotherapy.KEY WORDS: imatinib mesylate; paclitaxel; hypoxic;radiosensitivity; cervical cancer; human cervical cancer cell line Hela;Dissertation Type: Basic type for applicationIV第1章 综述宫颈癌是常见的妇科恶性肿瘤肿瘤之一，在发展中国家发病率较高。据 2000 年卫生部统计资料显示，我国每年宫颈癌的新增病例为 13.15 万人左右， 约占全部肿瘤患者的 1/3, 在全世界各类常见恶性肿瘤中仅次于胃癌、肺癌、乳 癌和大肠癌，居第 5 位，占全部恶性肿瘤的 7.3%。因此，宫颈癌的防治仍是妇 科肿瘤的重要课题之一。放射治疗在宫颈癌的治疗中占有重要地位。临床上，放 疗己经应用于各个期别的宫颈癌，但近年来其疗效的提高并不理想，据统计临床 Ⅰ、Ⅱ期患者放疗后 5 年生存率为 65%--85%；Ⅲ、Ⅳ期患者约 20%--50%，其 主要原因为放疗抵抗，而研究显示肿瘤内存在的乏氧细胞是导致肿瘤放疗抵抗的 主要原因之一。肿瘤乏氧不仅可影响体积较大并伴有广泛坏死的实体瘤的放化疗甚至手术治 疗的效果，甚至对那些早期的原发性肿瘤、复发转移性肿瘤和手术切缘残留癌的 治疗亦有影响。由于乏氧肿瘤细胞对放射治疗以及众多抗癌药物均有抵抗作用， 目前已经进行了大量的实验及临床研究来探讨抑制肿瘤细胞乏氧的方法。生物技 术的不断进步使我们可以根据肿瘤内氧的水平及变化来制定新的治疗策略，从而 使我们可以根据患者的个体差异选择治疗方案，使乏氧定向治疗成为可能。一个世纪以前，对于肿瘤及正常组织内血液流变学及氧含量变化的研究已经 开始，时至今日，随着分子生物技术及肿瘤乏氧病理生理学的发展，研究方法已 经有了较大的进步