| 摘要: |
| 目的：探讨扶正解毒祛瘀方（简称“扶正方”）联合奥沙利铂（oxaliplatin，L-OHP）对人结直肠癌 HT-29 裸鼠移植瘤的影响。方法：构建裸鼠移植性结直肠癌 HT-29 肿瘤模型，将其随机分为空白组、扶正方组、L-OHP 组及扶正方 + L-OHP 组，每组 10 只。空白组给予生理盐水灌胃，扶正方（50 g/kg）为灌胃给药；L-OHP（10 mg/kg）为腹腔注射给药（ip）1 次。扶正方 +L-OHP 组为 L-OHP 腹腔注射给药（ip）1 次，扶正方灌胃（ig）给药，每日 1 次，连续 21 d。观察扶正方对皮下移植瘤的作用及与 L-OHP 合用的效果；并用 RT-PCR 及 Western blotting 法检测细胞周期相关因子细胞周期素D1（cyclin D1）、细胞周期蛋白依赖激酶 4（CDK4）、增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）和细胞周期蛋白依赖性激酶抑制剂 P21（P21）的表达，比较各组的变化。结果：扶正方组、L-OHP 组、扶正方 +L-OHP 组的抑瘤率分别为 9.36%、29.69%、44.54%，均能抑制结肠癌移植瘤的生长。免疫器官脾的脏器指数空白组（0.41±0.04）、合用组（0.45±0.11），而扶正方组为（0.47±0.05），均高于 L-OHP 组（0.40±0.11）；且扶正方组显著高于空白组（P<0.01）。 PCR 与 Western blotting 结果均显示，与空白组比较，L-OHP 组、扶正方 +L-OHP 组 cyclin D1、CDK4、PCNA 的表达下调（P<0.05，P<0.01），P21 的表达上调（P<0.01）；与 L-OHP 组比较，扶正方 +L-OHP 组 PCNA（P<0.01）表达下调，P21的表达上调（P<0.01）。结论：扶正方与 L-OHP 单独和联合应用均对结肠癌小鼠移植瘤的生长有抑制作用，且两药合用不仅能增强化疗效果，同时在一定程度上抑制了 L-OHP 的毒性，其机制可能与影响周期相关因子的表达有关。 |
| 关键词: 扶正方 奥沙利铂 联合用药 人结肠癌 HT-29 抗肿瘤 |
| DOI：10.3969/j.issn.1007-6948.2019.04.036 |
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| 基金项目:天津市中医药管理局中医中西医结合科研课题（13164）；天津市滨海新区塘沽科技发展专项资金项目（2013MS05- 03）；天津市滨海新区卫生局一般扶持项目（2014BWKY014） |
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| Effect of Fuzheng Jiedu Quyu Formula and Oxaliplatin on Human Colorectal Cancer Transplanted in Nude Mice |
| ZHANG Gui-xian,ZHAO Xiu-mei,LIU Xiao-yun,LIU Hong-bin,ZHOU Bing,CHAI Zhong-qiu |
| Center for Research and Development of Antineoplastic Drugs, Tianjin Institute of Medical and Pharmaceutical Science, Tianjin (300020), China;Anorectal Department of Traditional Chinese Medicine Hospital, Binhai New District, Tianjin (Tianjin 300451) |
| Abstract: |
| Objective To investigate the effect of Fuzheng Jiedu Quyu formula (Fuzheng formula) combined with Oxaliplatin (L-OHP) on human colon cancer HT-29 cells in nude mice. Methods Mouse model of transplanted colon cancer HT-29 in nude mice was constructed. After tumor formation, they were randomly divided into 4 groups: blank group, Fuzheng formula group, L-OHP group and Fuzheng formula combined with L-OHP (Fuzheng+L-OHP) group, n=10 in each group. In the blank group, mice received normal saline injections throughout the entire 21 d study period, Fuzheng formula groupreceived intragastric administration of Chinese herb (50 g/kg), and L-OHP group were intraperitoneally (ip) given L-OHP (10 mg/kg) once. Fuzheng+L-OHP group were given intraperitoneal injection of L-OHP (ip) once, and intragastric (ig) administration of Fuzheng formula daily for 21 consecutive days. The effect of Fuzheng formula combined with L-OHP on the tumorinhibition rate of subcutaneous transplanted tumor was observed. The expression levels of cyclin D1, CDK4, PCNA and P21 in transplanted tumor were observed by RT-PCR and Western blotting, and the changes of each group were compared. Results The tumorinhibiting rates were 6 . 7 %, 26 . 7 % and 46 . 7 %, respectively in Fuzheng formula group, L-OHP group and Fuzheng+L-OHP group. All of these can inhibit the growth of colon cancer HT-29 transplantation tumor. The spleen index in blank group (0.41±0.04), combined group (0.45±0.11), and Fuzheng formula group (0.47±0.05) were higher than that in L-OHP group (0.40±0.11), and the Fuzheng formula group was significantly higher than that of blank group (P < 0 . 01). Results of RT-PCR indicated that, compared with blank group, the expression levels of cyclin D1, CDK4 and PCNA mRNA were down-regulated in Chinese medicine group, L-OHP group and Fuzheng+L-OHP group (P<0.05, P<0.01), and the expression level of P21 was up-regulated (P<0.01). As compared with the L-OHP group, the expression level of PCNA mRNA down-regulated in Fuzheng+L-OHP group (P<0.01), and the expression level of P21 was up-regulated (P<0.01). Results of Western blotting showed that, compared with blank group, the expression levels of cyclin D1, CDK4 and PCNA protein were down-regulated in Fuzheng formula group, L-OHP group and Fuzheng+L-OHP group (P<0.05, P<0.01), but the expression level of P21 was up-regulated (P<0.05); compared with the L-OHP group, the expression levels of Cyclin D1 and PCNA mRNA were down-regulated in Fuzheng+L-OHP group (P<0.01), and the expression of P 21 was up-regulated (P <0.01). Conclusion Fuzheng formula, L-OHP and their combination can inhibit the growth of transplanted tumors in mice with colon cancer and the combination of the two drugs can not only enhance the effect of chemotherapy, but also inhibit the toxicity of L-OHP to some extent. The mechanism may be related to the expression of cyclin D1, CDK4, PCNA and P21. |
| Key words: Fuzheng formula oxaliplatin drug combination human colon cancer HT-29 antitumor |
