中华核医学杂志
中華覈醫學雜誌
중화핵의학잡지
CHINESE JOURNAL OF NUCLEAR MEDICINE
2011年
2期
82-86
,共5页
陈道桢%唐秋莎%项静英%许飞%张立%王峻峰
陳道楨%唐鞦莎%項靜英%許飛%張立%王峻峰
진도정%당추사%항정영%허비%장립%왕준봉
乳腺肿瘤%肿瘤细胞,培养的%磁性纳米颗粒%基因疗法%近距离放射疗法%小鼠,裸
乳腺腫瘤%腫瘤細胞,培養的%磁性納米顆粒%基因療法%近距離放射療法%小鼠,裸
유선종류%종류세포,배양적%자성납미과립%기인요법%근거리방사요법%소서,라
Breast neoplasms%Tumor cells,cultured%Nano-magnetic particles%Gene therapy%Brachytherapy%Mice,nude
目的 观察纳米磁粒磁感应加热、单纯疱疹病毒-胸苷激酶(HSV-tk)基因及核素内照射联合治疗MCF-7乳腺癌的作用,探讨联合治疗的有效性与可行性.方法 制备转染试剂脂质体(Lipofectamine)/含热休克蛋白启动子的HSV-tk基因表达质粒(pHSP-HSV-tk)、四氧化三铁纳米磁流液、188Re-丙氧鸟苷白蛋白纳米微球(GCV-BSA-NP);进行四氧化三铁纳米磁流液的体内加热实验;建立MCF-7乳腺癌模型,并用单纯随机抽样法将60只荷瘤鼠分成6组,每组10只.A组为空白对照组,B组为单纯基因转染治疗组,C组为单纯热疗组,D组为基因转染联合核素内照射治疗组,E组为基因转染联合热疗组,F组为基因、热疗、核素内照射联合治疗组.各组经不同方法处理后,观察肿瘤生长情况,测肿瘤质量,观察肿瘤组织病理变化;RT-PCR法检测B、D、E、F组HSV-tk基因表达(与内参β-actin mRNA吸光度比值)情况.各组与对照组比较采用泊松分布及单因素方差分析,所用统计软件为SPSS 10.0.结果 在动物体内加热实验中,交变磁场(AMF)作用下,不同注射剂量磁粒都引起肿瘤组织温度快速升高,2,4和6 mg磁粒分别使肿瘤温度升至39.6 ℃,43.2 ℃和48.1 ℃,且持续40 min.当AMF作用停止后,肿瘤组织温度10 min内分别降至36.8 ℃,37.5 ℃和37.8 ℃.成功建立MCF-7乳腺癌模型,治疗结果显示:C、D、E、F组肿瘤质量[(452.50±30.29)、(240.98±35.32)、(231.87±27.41)、(141.55±23.78)mg]较A组[(719.12±22.65)mg]差异有统计学意义(F=800.007,P＜0.01),且以F组疗效最好;C组与E组肿瘤质量大于F组,差异有统计学意义(t=25.533,7.872,P均＜0.05);D组较B组肿瘤质量明显减小,且差异有统计学意义(t=32.805,P＜0.05).RT-PCR半定量分析显示:B、D组的表达量(0.33±1.30,0.46±0.12)与E、F组(0.66±0.13,0.74±0.11)相比差异有统计学意义(F=21.573,P＜0.05).结论 热疗、基因治疗联合核素治疗能有效抑制MCF-7乳腺癌的生长,对乳腺癌治疗有潜在的应用前景.
目的 觀察納米磁粒磁感應加熱、單純皰疹病毒-胸苷激酶(HSV-tk)基因及覈素內照射聯閤治療MCF-7乳腺癌的作用,探討聯閤治療的有效性與可行性.方法 製備轉染試劑脂質體(Lipofectamine)/含熱休剋蛋白啟動子的HSV-tk基因錶達質粒(pHSP-HSV-tk)、四氧化三鐵納米磁流液、188Re-丙氧鳥苷白蛋白納米微毬(GCV-BSA-NP);進行四氧化三鐵納米磁流液的體內加熱實驗;建立MCF-7乳腺癌模型,併用單純隨機抽樣法將60隻荷瘤鼠分成6組,每組10隻.A組為空白對照組,B組為單純基因轉染治療組,C組為單純熱療組,D組為基因轉染聯閤覈素內照射治療組,E組為基因轉染聯閤熱療組,F組為基因、熱療、覈素內照射聯閤治療組.各組經不同方法處理後,觀察腫瘤生長情況,測腫瘤質量,觀察腫瘤組織病理變化;RT-PCR法檢測B、D、E、F組HSV-tk基因錶達(與內參β-actin mRNA吸光度比值)情況.各組與對照組比較採用泊鬆分佈及單因素方差分析,所用統計軟件為SPSS 10.0.結果 在動物體內加熱實驗中,交變磁場(AMF)作用下,不同註射劑量磁粒都引起腫瘤組織溫度快速升高,2,4和6 mg磁粒分彆使腫瘤溫度升至39.6 ℃,43.2 ℃和48.1 ℃,且持續40 min.噹AMF作用停止後,腫瘤組織溫度10 min內分彆降至36.8 ℃,37.5 ℃和37.8 ℃.成功建立MCF-7乳腺癌模型,治療結果顯示:C、D、E、F組腫瘤質量[(452.50±30.29)、(240.98±35.32)、(231.87±27.41)、(141.55±23.78)mg]較A組[(719.12±22.65)mg]差異有統計學意義(F=800.007,P＜0.01),且以F組療效最好;C組與E組腫瘤質量大于F組,差異有統計學意義(t=25.533,7.872,P均＜0.05);D組較B組腫瘤質量明顯減小,且差異有統計學意義(t=32.805,P＜0.05).RT-PCR半定量分析顯示:B、D組的錶達量(0.33±1.30,0.46±0.12)與E、F組(0.66±0.13,0.74±0.11)相比差異有統計學意義(F=21.573,P＜0.05).結論 熱療、基因治療聯閤覈素治療能有效抑製MCF-7乳腺癌的生長,對乳腺癌治療有潛在的應用前景.
목적 관찰납미자립자감응가열、단순포진병독-흉감격매(HSV-tk)기인급핵소내조사연합치료MCF-7유선암적작용,탐토연합치료적유효성여가행성.방법 제비전염시제지질체(Lipofectamine)/함열휴극단백계동자적HSV-tk기인표체질립(pHSP-HSV-tk)、사양화삼철납미자류액、188Re-병양조감백단백납미미구(GCV-BSA-NP);진행사양화삼철납미자류액적체내가열실험;건립MCF-7유선암모형,병용단순수궤추양법장60지하류서분성6조,매조10지.A조위공백대조조,B조위단순기인전염치료조,C조위단순열료조,D조위기인전염연합핵소내조사치료조,E조위기인전염연합열료조,F조위기인、열료、핵소내조사연합치료조.각조경불동방법처리후,관찰종류생장정황,측종류질량,관찰종류조직병리변화;RT-PCR법검측B、D、E、F조HSV-tk기인표체(여내삼β-actin mRNA흡광도비치)정황.각조여대조조비교채용박송분포급단인소방차분석,소용통계연건위SPSS 10.0.결과 재동물체내가열실험중,교변자장(AMF)작용하,불동주사제량자립도인기종류조직온도쾌속승고,2,4화6 mg자립분별사종류온도승지39.6 ℃,43.2 ℃화48.1 ℃,차지속40 min.당AMF작용정지후,종류조직온도10 min내분별강지36.8 ℃,37.5 ℃화37.8 ℃.성공건립MCF-7유선암모형,치료결과현시:C、D、E、F조종류질량[(452.50±30.29)、(240.98±35.32)、(231.87±27.41)、(141.55±23.78)mg]교A조[(719.12±22.65)mg]차이유통계학의의(F=800.007,P＜0.01),차이F조료효최호;C조여E조종류질량대우F조,차이유통계학의의(t=25.533,7.872,P균＜0.05);D조교B조종류질량명현감소,차차이유통계학의의(t=32.805,P＜0.05).RT-PCR반정량분석현시:B、D조적표체량(0.33±1.30,0.46±0.12)여E、F조(0.66±0.13,0.74±0.11)상비차이유통계학의의(F=21.573,P＜0.05).결론 열료、기인치료연합핵소치료능유효억제MCF-7유선암적생장,대유선암치료유잠재적응용전경.
Objective To investigate the antitumor therapeutic effect of combined therapy of magnetic induction heating by nano-magnetic particles, herpes simplex virus thymidine kinase gene(HSV-tk suicide gene) and internal radiation in mice bearing MCF-7 breast carcinoma. Methods The transfection reagents, plasmids heat shock protein-HSV-tk (pHSP-HSV-tk), ferroso-ferric oxide nano-magnetic fluid flow and 188Re-ganciclovir-bovine serum albumin-nanopaticles (GCV-BSA-NP) were prepared. The heating experiments in vivo were carried out using ferroso-ferric oxide nano-magnetic fluid flow. Sixty mice tumor models bearing MCF-7 breast carcinoma were established and randomly divided into six groups. Group A was the control group, B was gene transfection therapy group, C was hyperthermia group, D was gene transfection therapy combined with radionuclide brachytherapy group, E was gene therapy combined with hyperthermia group, and F was gene therapy, hyperthermia combined with radionuclide brachytherapy group. The tumor growth, tumor mass and histopathological changes were evaluated. The expression of HSV-tk in the groups of B, D, E and F was detected by RT-PCR. Poisson distribution and one-way analysis of variance (ANOVA) were used for statistical analysis by SPSS 10.0 software. Results In the animal heating experiments, the temperature of tumor increased up to 39.6 ℃, 43.2 ℃, and 48.1 ℃ quickly with different injected doses (2, 4 and 6 mg respectively) of nano-magnetic particles and maintained for 40 min. The temperature of tumor tissue reduced to 36.8 ℃, 37.5 ℃ and 37.8 ℃ in 10 min when alternating magnetic field (AMF) stopped. The tumor mass in Groups C ((452.50 ±30.29) mg), D ((240.98 ±35.32)mg), E((231.87 ±27.41) mg) and F ((141.55 ±23.78) mg) were much lower than that in Group A ((719.12±22.65) mg) (F=800.07, P＜0. 01), with the most significant treatment effect in Group F.The tumor mass in Group B((684.05 ±24.02) mg) was higher than that in Group D (t =32. 805, P ＜0. 05). Semi-quantitative RT-PCR analysis showed that the expression of HSV-tk in Groups B and D (0.33 ±0. 13 and 0. 46 ±0.12) was significantly different from that in Groups E and F (0.66 ±0.13 and 0.74 ±0. 11)(F = 21. 573, P ＜ 0.05). Conclusion Combined use of hyperthermia, gene therapy and radionuclide brachytherapy could effectively depress the growth of MCF-7 breast carcinoma, thus possessing treatment potential for this tumor.
