Molecular mechanisms in radiation-induced cell death of gynecologic cancer

(I)细胞因子和抗癌药物对人宫颈鳞癌放射敏感性的影响。INFS和抗Fas-IgM增强放射诱导的宫颈鳞癌细胞死亡，而IL-1β和转化生长因子-β1呈剂量依赖性抑制细胞死亡。转化生长因子-β1而不是IL-1β的抑制机制是组织特异性和细胞周期依赖性的。(2)建立了人宫颈鳞癌细胞辐射抗性亚克隆的建立和鉴定，并进行了抗癌药物敏感性试验。抗辐射细胞对CDDP、SN38或THP的敏感性较高，提示放疗后复发的宫颈鳞癌患者应选用这些药物。(3)人宫颈鳞癌细胞抗癌耐药亚克隆的建立及鉴定。几个耐药的亚克隆对几种抗癌药物和伽马射线表现出交叉耐药性。3个抗CPA的亚克隆均能抵抗辐射诱导的细胞死亡。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。我们的结果表明，癌细胞获得性耐药可能与获得放射抗性有关；相反，这表明癌细胞获得放射耐药性可能与获得性耐药有关。半定量RT-PCR分析结果表明，bcl2家族基因产物c-myc和β-肌动蛋白可能对人宫颈鳞癌细胞具有共同的凋亡信号。因此，可以推断，这些突变可以作为遗传标记来评估宫颈癌细胞的耐药性和/或放射耐药性。

(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.