中华放射肿瘤学杂志
中華放射腫瘤學雜誌
중화방사종류학잡지
CHINESE JOURNAL OF RADIATION ONCOLOGY
2010年
4期
358-363
,共6页
欧广飞%坂坂聪%曾丽华%涩谷景子%易俊林%原田浩%平冈真宽
歐廣飛%坂坂聰%曾麗華%澀穀景子%易俊林%原田浩%平岡真寬
구엄비%판판총%증려화%삽곡경자%역준림%원전호%평강진관
细胞系,肺肿瘤%肿瘤移植,裸鼠%贝伐单抗%放射
細胞繫,肺腫瘤%腫瘤移植,裸鼠%貝伐單抗%放射
세포계,폐종류%종류이식,라서%패벌단항%방사
Cell lines,lung neoplasm%Neoplasm xenografts,mice%Bevacizumab%Irradiation
目的 实时测定贝伐单抗和放射线作用人肺腺癌细胞系(NCI-H141)裸鼠移植瘤后活体乏氧调节蛋白(HIF-1α)水平变化,为优化贝伐单抗和放射线联合计划提供依据.方法 用HIF-1α荧光蛋白报告质粒转染NCI-H441细胞连续测定肿瘤乏氧水平,并观察贝伐单抗与放射线(122Scγ射线)早晚联合后HIF-1α水平变化、血管数量和渗透性、肿瘤反应、乏氧分子标记、凋亡率和肿瘤生长延迟的异同.结果 单纯贝伐单抗作用后24 h肿瘤HIF-1α表达水平较对照组轻度下降(3.1×106:6.1×106;t=-1.73,P>0.05),功能血管密度升高(16.6:12.1;t=-1.40,P>0.05)和血管渗透指标明显改善(2.9%:11.5%;t=6.80,P<0.01);随后HIF-1α表达水平迅速升高(7.4×106:20.4×106;t=2.36,P<0.05)并维持至疗后8～10 d(第3天时高于对照组3～4倍)且总血管密度明显下降(37.4:15.9;t=5.36,P<0.01).贝伐单抗治疗72 h后联合放射线作用组比24 h后联合作用组肿瘤血管记数高(联合作用后第3天,9.33:3.17;t=-2.43,P<0.05)、凋亡记数低(联合作用后第3天,23.33:43.83;t=2.54,P<0.05),生长延迟时间也明显缩短(10.5:23.0;t=2.67,P<0.05).结论 贝伐单抗联合放射线作用后72 h贝伐单抗诱导的乏氧对血管和肿瘤细胞具有明显的放射抵抗作用,提示血管靶向药物联合放射作用可能存在时间增益窗口.
目的 實時測定貝伐單抗和放射線作用人肺腺癌細胞繫(NCI-H141)裸鼠移植瘤後活體乏氧調節蛋白(HIF-1α)水平變化,為優化貝伐單抗和放射線聯閤計劃提供依據.方法 用HIF-1α熒光蛋白報告質粒轉染NCI-H441細胞連續測定腫瘤乏氧水平,併觀察貝伐單抗與放射線(122Scγ射線)早晚聯閤後HIF-1α水平變化、血管數量和滲透性、腫瘤反應、乏氧分子標記、凋亡率和腫瘤生長延遲的異同.結果 單純貝伐單抗作用後24 h腫瘤HIF-1α錶達水平較對照組輕度下降(3.1×106:6.1×106;t=-1.73,P>0.05),功能血管密度升高(16.6:12.1;t=-1.40,P>0.05)和血管滲透指標明顯改善(2.9%:11.5%;t=6.80,P<0.01);隨後HIF-1α錶達水平迅速升高(7.4×106:20.4×106;t=2.36,P<0.05)併維持至療後8～10 d(第3天時高于對照組3～4倍)且總血管密度明顯下降(37.4:15.9;t=5.36,P<0.01).貝伐單抗治療72 h後聯閤放射線作用組比24 h後聯閤作用組腫瘤血管記數高(聯閤作用後第3天,9.33:3.17;t=-2.43,P<0.05)、凋亡記數低(聯閤作用後第3天,23.33:43.83;t=2.54,P<0.05),生長延遲時間也明顯縮短(10.5:23.0;t=2.67,P<0.05).結論 貝伐單抗聯閤放射線作用後72 h貝伐單抗誘導的乏氧對血管和腫瘤細胞具有明顯的放射牴抗作用,提示血管靶嚮藥物聯閤放射作用可能存在時間增益窗口.
목적 실시측정패벌단항화방사선작용인폐선암세포계(NCI-H141)라서이식류후활체핍양조절단백(HIF-1α)수평변화,위우화패벌단항화방사선연합계화제공의거.방법 용HIF-1α형광단백보고질립전염NCI-H441세포련속측정종류핍양수평,병관찰패벌단항여방사선(122Scγ사선)조만연합후HIF-1α수평변화、혈관수량화삼투성、종류반응、핍양분자표기、조망솔화종류생장연지적이동.결과 단순패벌단항작용후24 h종류HIF-1α표체수평교대조조경도하강(3.1×106:6.1×106;t=-1.73,P>0.05),공능혈관밀도승고(16.6:12.1;t=-1.40,P>0.05)화혈관삼투지표명현개선(2.9%:11.5%;t=6.80,P<0.01);수후HIF-1α표체수평신속승고(7.4×106:20.4×106;t=2.36,P<0.05)병유지지료후8～10 d(제3천시고우대조조3～4배)차총혈관밀도명현하강(37.4:15.9;t=5.36,P<0.01).패벌단항치료72 h후연합방사선작용조비24 h후연합작용조종류혈관기수고(연합작용후제3천,9.33:3.17;t=-2.43,P<0.05)、조망기수저(연합작용후제3천,23.33:43.83;t=2.54,P<0.05),생장연지시간야명현축단(10.5:23.0;t=2.67,P<0.05).결론 패벌단항연합방사선작용후72 h패벌단항유도적핍양대혈관화종류세포구유명현적방사저항작용,제시혈관파향약물연합방사작용가능존재시간증익창구.
Objective To evaluate the impact of the hypoxia induced by bevacizumab on the antitumor effect in combining with irradiation in CNI-H441 xenografts in mice. Methods Bevacizumab of 5 mg/kg mouse for groups of control, bevacizumab alone, irradiation alone, earlier combination (EC), and later combination (LC) were initially injected peritoneally. Single irradiation of 14 Gy (122Sc γ-ray) was given at the 4th hour for the group of irradiation alone, 24th hour for EC group, and 72nd hour for LC group after the initial injection. Tumor hypoxia, micro vessels density and permeability of tumor vasculature,pathological responses, apoptosis, and tumor growth delay curve were evaluated after using bevacizumab and/or irradiation. Results Although it was lower than the control at the 24 hr after using bevacizumab (3. 1 × 106: 6.1 × 106 ;t = - 1.73 ,P > 0. 05), the HIF-1α rapidly increased to 3 - 4 times and 2 - 3 times of the control at day 3 (7.4 × 106: 20. 4 × 106; t = 2. 36, P < 0. 05) and lasted until day 10, which was consistent with the changes of tumor function vessels count. The count of residual micro vessel density count in LC group was higher than that in groups of EC and irradiation at day 3 after irradiation (9. 33: 3. 17;t =- 2. 43, P < 0. 05). The apoptotic count of tumor cells was lower in LC group than that in EC group (23.33: 43.83; t= 2.54, P< 0.05, at day 3 after radiation). Tumor growth delay time of LC groupwas shorter than that of EC groups (10. 5 days vs. 23. 0 days , t = 2. 67 , P < 0. 05) . Conclusions Hypoxia level induced by bevacizumab decreases the antitumor effect in later combination of bevacizumab and irradiaion. It shows a time window that determines whether the combination of bevacizumab and irradiation will be benefit or diverse.
