紫杉醇脂质体节奏性化疗对胃癌乏氧影响的实验研究

Experimental Study of Effects of Metronomic Chemotherapy with Paclitaxel-Liposomes on Gastric Cancer Hypoxia

[目的]利用乏氧显像监测紫杉醇脂质体节奏性化疗过程中胃癌的乏氧变化。[方法]36只荷人胃癌HS-746T细胞的雄性裸鼠(4～6周)随机分成两组,治疗组按5mg/kg的剂量每3天一次行腹腔内注射紫杉醇脂质体,对照组注射同体积的生理盐水。治疗后第2d和14d利用SPECT全身静态扫描显示注射99mTc-HL91后5,10,15,30,60,120和180min的显像。在显像上标记感兴趣区为靶点,计算各组靶/非靶比值。然后处死裸鼠、切下肿瘤行称重和放射性计数。通过免疫组织化学染色检测CD34表达,计算肿瘤微血管密度(MVD)。[结果]治疗后第2d,紫杉醇脂质体治疗组T/NT低于对照组(7.82±0.28vs.9.56±0.31,P<0.05),离体肿瘤放射性滞留降低(0.71±0.03vs.0.97±0.03,P<0.05),MVD降低(42.89±2.63vs.52.78±3.09,P<0.05);治疗后第14d,治疗组T/NT高于对照组(11.54±0.42vs.9.96±0.28,P<0.05),离体肿瘤放射性滞留升高(1.42±0.05vs.11.54±0.42,P<0.05),MVD明显降低(27.89±2.51vs.66.11±2.83,P<0.001)。[结论]治疗初期紫杉醇脂质体降低胃癌乏氧,后期乏氧增加,乏氧监测对胃癌的治疗有一定的指导意义。

[Purpose] To monitor the hypoxic change of gastric cancer during metronomic chemotherapy with paclitaxel-liposomes by the hypoxia imaging. [Methods ] Thirty-six male nude mice bearing human gastric cancer HS-746T cells were randomly divided into two groups： The treatment group received paclitaxel-liposomes at a dose of 5mg/kg intraperitoneally and control group received the same volume of saline in every three days. On 2 and 14 days, all the mice underwent static whole body planar imaging with SPECT at 5, 10, 15, 30, 60, 120 and 180 minutes after injection of ^99mTc-HL91. Region of interest, ROI were drawn as the target in planar imagines and target-to-non targeted （T/NT） were calculated. Then the mice were sacrificed and the tumors were removed, weighted and the radioactivities were measured. CD34 expressions were detected by immunohistochemical staining and microvascular densities （MVD） of the tumors were calculated. [Results] On the second days after paclitaxel-liposomes treatment, T/NT ratio of treatment group was significantly lesser than that of control group （7.82±0.28 vs. 9.56±0.31, P〈0.05）, the radioactive retention and the MVDs of isolated tumor tissues in the treatment group were lesser than those of control （0.71±0.03 vs. 0.97±0.03,P〈0.05） （42.89± 2.63 vs. 52.78±3.09,P〈0.05）. On 14 days after treatment, T/NT ratio and the radioactive retention of treatment group were significantly higher than those of control group （11.54±0.42 vs. 9.96±0.28,P〈 0.05） （1.42±0.05 vs. 11.54±0.42,P〈0.05）. The MVD of isolated tumor tissues in the treatment group was significantly lesser than that in control （27.89±2.51 vs. 66.11 ±2.83,P〈0.001 ）. [Conclusion]In the early stage of the treatment, paclitaxel-liposomes decrease the hypoxia of gastric cancer and in the late stage of treatment which increases the tumor hypoxia. Therefore, detection tumor hypoxia may be important in guiding the treatment for gastric cancer.