摘要
目的运用磁共振氢质子频谱(Proton MRS,1H-MRS)分析研究rAd/p53治疗人类结肠癌荷瘤裸鼠的早期改变,探索1H-MRS活体无创评价rAd/p53早期抗癌疗效的标记物。方法 50只人类结肠癌SW480荷瘤BALB/c裸小鼠随机分成两组:对照组,rAd/P53治疗组。于假治疗或治疗后24h、48h、72h、120h、168h各组分别随机取5只荷瘤鼠行1H-MRS。随后处死荷瘤鼠,即切下肿瘤,检测肿瘤的p53蛋白表达(Western blot)、凋亡(TUNNEL)。结果 24h:CHO/CR面积比及GLX β～γ/CR面积比较对照组减少(P<0.05);48h:Lip峰高及面积较对照组增加(P<0.05);72h以上:GLX β～γ/CR面积比较对照组减少(P<0.05);120h以上:GLXα/CR面积比较对照组减少(P<0.05)。三个治疗组在观察时间点肿瘤坏死、凋亡范围较对照组增加,p53蛋白表达均较对照组增高。CR面积、Lip峰高和面积与肿瘤细胞凋亡呈正相关;GLX β～γ/CR的面积比、GLX α/CR的面积比与肿瘤细胞凋亡呈负相关。结论 rAd/p53治疗肿瘤早期CHO/CR、GLXα/CR与GLX β～γ/CR面积比出现降低,Lip出现增加,与肿瘤细胞的凋亡增加相关,可作为肿瘤治疗早期疗效评价的生物标志物。
Objective To observe therapeutic response of rAd/p53 in human colon cancer model using Proton magnetic resonance spectroscopy （IH-MRS） and investigate biomarkers of early response to tAd/p53 with 1H-MRS. Methods The tumor pieces of human colon cancer SW480 were implanted subcutaneously in 50 nude mice. These mice were divided randomly into two groups and administrated with NS, rAd/p53 by intra-tumoral injection. At 24 h, 48 h, 72 h, 120 h, 168 h after treatment, 5 mice each group were performed XH-MRS, then theirs tumors were removed. P53 expression （Western blot） and apoptosis oftttmor （TUNNEL） were assessed. Results At 24 h, the area ratio of CHO/CR and GLXβ-γ/CR were less than that of control group （P 〈0.05）. At 48 h, the Lip peak height and area were more than that of control group （P 〈0.05）. More than 72 h, the area ratio of GLX β-γ/CR were less than that of control group （P 〈0.05）. More than 120 h, the area ratio of GLX α/CR were less than that of control group （P 〈0.05）. P53 expression and apoptosis of tumor in therapy groups was higher than control group. The CR area and the Lip peak height ＆ area showed positive correlations with the percentage of tumor cell apoptosis. The area ratio of GLX β-γ/CR and the area ratio of GLX α/CR showed negative correlations with the percentage of tumor cell apoptosis. Conclusions In the early treatment of tumor, the area ratio of CHO/CR, GLXα/CR and GLXβ-γ/CR decreased, but Lip increased, these variables correlated with percentage of tumor cell apoptosis. They can be used as the biomarker of early detection of tumor response.
出处
《临床医学工程》
2012年第9期1460-1462,共3页
Clinical Medicine & Engineering
基金
广东省社会发展领域科技计划项目(2010B031600013)
广州市科技计划项目(2010y1-c391)
项目负责人:谢琦
