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Molecular mechanisms in radiation-induced cell death of gynecologic cancer

放射诱导妇科癌症细胞死亡的分子机制

基本信息

批准号：
09671708
负责人：
TANAKA Tetsuji
金额：
$ 1.92万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

(I) Effects of cytokines and anticancer drugs on radiosensitivities of radiosensitive human cervical SCC cells. INFs and anti-Fas IgM enhanced radiation-induced cell death in the cervical SCC cells, while IL-1beta and TGF-beta1 inhibited the cell death dose-dependently. The inhibitory mechanisms by TGF-beta1, not by IL-1beta, were shown to be tissue-specific and cell cycle-dependent manners.(2) Establishment and characterization of radioresistant subclones derived from the human cervical SCC cells Radioresistant subolones were established and examined for anticancer drug-sensitivity tests. The result that the radioresistant cells had higher sensitivities to CDDP, SN38, or THP indicates that these drugs should be chosen for the patients with postirradiation recurrent cervical SCC.Expression cloning experiments of the radioresistant genes were tried in vain.(3) Establishment and characterization of anti cancer drug-resistant subclones derived from the human cervical SCC cells. Several drug-resistant subclones exhibited cross-resistances to several anticancer drugs and gamma-irradiation. Three CPA-resistant subclones were resistant to radiation-induced cell death. This suggests a possibility that CPA-induced apoptosis share common signaling pathways to radiation-induced apoptosis in the SCC cells. Our results indicate that acquired drug-resistance in cancer cells might be associated with acquisition of radioresistance ; and conversely this indicates that acquisition of radio-resistance in cancer cells might be associated with acquired drug-resistance. Results of the semi-quantitative RT-PCR analyses suggest a possibility that bcl-2 family gene products, c- myc, and beta-actin share some common apoptotic signals to human cervical SCC cells. Accordingly it is thus inferred that these mutations can be used for genetic markers to evaluate drug-resistance and/or radio-resistance in cervical cancer cells.

(I)细胞因子和抗癌药物对放射敏感的人宫颈鳞癌细胞放射敏感性的影响。INF和抗Fas IgM增强了宫颈鳞癌细胞辐射诱导的细胞死亡，而IL-1 β和TGF-β 1剂量依赖性地抑制细胞死亡。TGF-β 1而非IL-1 β的抑制机制显示出组织特异性和细胞周期依赖性。(2)人宫颈鳞状细胞癌放射抗性亚克隆的建立和鉴定放射抗性亚克隆被建立并用于抗癌药物敏感性试验。结果表明，放射抵抗细胞对顺铂、SN 38、THP等药物敏感性较高，提示放射后复发的宫颈鳞癌患者应选择这些药物治疗。(3)人宫颈鳞癌细胞抗肿瘤耐药亚克隆的建立及鉴定。几个耐药亚克隆对几种抗癌药物和γ射线表现出交叉耐药性。三个CPA抗性亚克隆对辐射诱导的细胞死亡具有抗性。这表明CPA诱导的细胞凋亡可能与辐射诱导的SCC细胞凋亡具有共同的信号通路。我们的研究结果表明，在癌细胞中获得的耐药性可能与获得的辐射抗性有关;相反，这表明在癌细胞中获得的辐射抗性可能与获得的耐药性有关。半定量RT-PCR分析的结果提示bcl-2家族基因产物、c-myc和β-actin可能与人宫颈SCC细胞共享一些共同的凋亡信号。因此，推断这些突变可用于遗传标记，以评估宫颈癌细胞的耐药性和/或放射抗性。