Radio- or chemo-sensitivity and analysis of gene transduction for induction of apoptosis for human tumor cell

放射或化学敏感性以及诱导人肿瘤细胞凋亡的基因转导分析

• 批准号: 08671007
• 负责人: SAITO Yoshihiro
• 金额: $ 1.34万
• 依托单位: Gunma University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671007/
• 关键词: radiosensitivity; chemosensitivity; apoptosis; paclitaxl; combination therapy of radiation with chemotherapy; supra-additive effect; Apoptosis; Radiosensitivity; Chemosensitivity; Paclitaxol; Taxol

Apoptotic death is reported to be important factor for radio- or chemo-sensitivity to tumor.Purpose is to investigate the differences between two rat yolk sac tumour cell lines with different radiosensitivities by different induction of apoptotic cells in paclitaxl sensitivity and in the sensitizing effects of paclitaxl in combination with irradiation. NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. Clonogenic assay demonstrated almost the same paclitaxl sensitivity with Do of 5.15 nM in NMT-1 and 5.02 nM in NMT-1R.Many apoptotic cells and DNA ladder formations were observed at 24 h after exposure to paclitaxl in both cell lines. The incidences of DNA fragmentation after 24 h exposure to 20 nM paclitaxl were 12.4 (]SY.+-。[) 3.3 % for NMT-1, and 13.0(]SY.+-。[) 1.9 % for NMT-1R.Paclitaxl showed a supra-additive effect in combination with radiation in both cell lines at 12 h after paclitaxl treatment only when the accumulation of cells in the G2M phase reached its peak.Paclitaxl had the same degree of cytotoxic effect in two cell lines with different radiosensitivity due to the induction of apoptosis. A supra-additive effect to radiation was observed with 12 h pretreatment in both cell lines. Paclitaxl may be effective for tumors with a component of different radiosensitivity in combination with irradiation.

细胞凋亡是肿瘤对放射或化疗敏感性的重要因素，目的研究两种不同放射敏感性的大鼠卵黄囊瘤细胞系对紫杉醇敏感性的差异以及紫杉醇与放射联合应用的增敏作用。NMT-1是亲本放射敏感细胞系，NMT-1 R是变体放射抗性细胞系。NMT-1和NMT-1 R细胞对紫杉醇的敏感性相近，DO分别为5.15 nM和5.02 nM。20 nM紫杉醇作用24小时后DNA断裂的发生率为12.4（± SD）。[）NMT-1为3.3%，[]SY. ±-为13.0。紫杉醇与放射联合作用于两种细胞株均表现出超累加效应，且仅在G2 M期细胞聚集达到高峰时才表现出超累加效应，紫杉醇对两种放射敏感性不同的细胞株均表现出相同程度的细胞毒效应，其原因是紫杉醇诱导细胞凋亡。在两种细胞系中观察到12 h预处理对辐射的超累加效应。紫杉醇联合放疗对不同放射敏感性的肿瘤可能有效。

项目成果

Saito Yoshihiro: "Cytotoxic effect of paclitaxl (taxol) either alone or in combination with irradiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro" International Journal of Radiation Biology. 73・2. 225-231 (1998)

Saito Yoshihiro：“紫杉醇（紫杉醇）单独或与体外放射敏感性不同的两种大鼠卵黄囊肿瘤细胞系的细胞毒性作用”国际放射生物学杂志73·2（1998）。

Saito Yoshihiro: "Cytotoxic effect of paclitaxl (taxol) or in combination with radiation in two rat yolk sac tumor cell lines with different radiosensitivities" Jpn.J.Cancer Clin.44-2. 243-244 (1998)

Saito Yoshihiro：“紫杉醇（紫杉醇）或与辐射组合对两种具有不同放射敏感性的大鼠卵黄囊肿瘤细胞系的细胞毒性作用”Jpn.J.Cancer Clin.44-2。

斉藤 吉弘: "放射線感受性の異なる腫瘍細胞株に対するpaclitaxel(Taxol)と放射線との併用効果" 癌の臨床. 44・2. 243-244 (1998)

Yoshihiro Saito：“联合使用紫杉醇（紫杉醇）和放射线对不同放射敏感性肿瘤细胞系的影响”癌症诊所 44・2（1998）。