Experiment of Different Administration Sequences of Apatinib and Paclitaxel on Lung Cancer
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摘要:目的
观察阿帕替尼联合紫杉醇不同时序给药对肺癌的抗肿瘤效应。
方法建立裸鼠A549肺癌模型，随机分成6组。A：0.9%氯化钠溶液组（0.9%NS, d1~8）。B：单用阿帕替尼组（APa, d1~7）。C：单用紫杉醇组（PTX, d1）。D：联合用药组1（C1组：PTX, d1；APa, d2~8）。E：联合用药组2（同时用药组，C2组：PTX, d1；APa, d1~7）。F：联合用药组3（C3组：APa，D1~7；PTX, d8），治疗结束次日行PET/CT扫描测肿瘤组织SUV值、ELISA检测血中VEGFR-2浓度、免疫组织化学检测肿瘤组织微血管计数、TUNEL法检测肿瘤组织细胞凋亡，绘制肿瘤生长曲线，计算肿瘤抑制率。
结果治疗组移植瘤生长速率较0.9%氯化钠溶液组均有所减慢（P < 0.05），联合用药组间抑瘤率差异无统计学意义，联合用药组2凋亡细胞数最多，VEGFR-2浓度、SUV值最低（P < 0.05），联合用药组2 MVD-CD31表达最低，与除联合用药组3外的其余各组比较，差异均有统计学意义（P < 0.05）。
结论阿帕替尼联合紫杉醇同时用药对肺癌治疗效果最好。
Abstract:ObjectiveTo observe the anti-tumor effect of apatinib(APa) combined with paclitaxel(PTX) at different sequential dosing on lung cancer.
MethodsA549 lung cancer nude mice model was established and randomly divided into six groups: A: Control group (0.9% NS, D1-8); B: Apatinib alone group (APa, D1-7); C: Paclitaxel alone group (PTX, D1); D: Combined group 1 (PTX, D1; APa, D2-8); E: Combined group 2 (PTX, D1; APa, D1-7); F: Combinaed group 3 (APa, D1-7; PTX, D8). The day after the end of treatment, we used ELISA to detect the VEGFR2 concentration of blood, immunohistochemistry was used to measure the microvessel number, TUNEL assay was employed to detect the apoptosis cells of tumor, and PET/CT was used to probe SUV value. We observed and drew the tumor growth curve, and then calculated the tumor inhibition rate.
ResultsThe tumor growth rate of treatment groups were all significantly slowed, compared with the physiological saline group (P < 0.05), and the tumor inhibition rate of all combined groups had no statistically significance compared with each other, respectively. The Combined group 2 showed most apoptotic cells, lowest VEGFR-2 levels and SUV value (P < 0.05), while the lowest MVD-CD31 expression in Combined group 2 had statistically significance compared with the physiological saline group, except the Combined group 3 (P < 0.05).
ConclusionApatinib combined with paclitaxel shows the best effect on treating lung cancer.
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Key words:
- Apatinib /
- Paclitaxel /
- Sequential dosing /
- Anti-angiogenesis therapy /
- Lung cancer
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图 1 阿帕替尼与紫杉醇不同时序给药联合方式
Figure 1 Apatinib(APa) combined with paclitaxel(PTX) at different sequential dosing
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图 3 免疫组织化学法检测各组微血管计数
Figure 3 Microvessel counts detected by immunohistochemical method
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图 4 Tunel法检测肿瘤组织细胞凋亡及其统计图
Figure 4 Tumor cells apoptosis detected by TUNEL assay and its statistical figure
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图 5 小动物PET/CT小鼠肿瘤图像及各组SUV值统计图
Figure 5 Micro PET/CT image of tumor bearing mice and statistical figure of SUV value in each group
表 2 ELISA法检测各组VEGFR-2水平的比较
Table 2 Statistical table of VEGFR-2 levels in each group detected by ELISA
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