Feng-liao-chang-wei-kang is synergistic with 5-fluorouracil in inhibiting proliferation of colorectal cancer
Feng-liao-chang-wei-kang is synergistic with 5-fluorouracil in inhibiting proliferation of colorectal cancer
复制标题
风抑肠胃康与5-氟尿嘧啶协同抑制结直肠癌增殖
DOI：
10.4103/1995-7645.271979
复制
发表时间：
2019-12-01
影响因子：
3.1
通讯作者：
Huang, Ling
中科院分区：
文献类型：
--
作者：
Ni, Pan-li;Tian, Shu-hong;Huang, Ling
目的：探讨风辽肠胃康对急、慢性胃肠炎的治疗作用，以及与5-氟尿嘧啶(5-FU)对结直肠癌生长抑制的协同作用及其机制。方法：体外实验中，将HT-29细胞分为5-FU单独给药组、FLCWK单独给药组和联合给药组。采用四甲基偶氮唑盐比色法检测细胞增殖情况，流式细胞仪检测细胞周期变化，建立结直肠癌裸鼠皮下移植瘤模型。所有小鼠按体重随机分为5-FU组、FLCWK组和联合给药组。在给药过程中，使用交互式视频信息系统小动物实时成像系统监测裸鼠皮下移植的生长情况。用BALB/c小鼠建立结肠炎相关性结直肠癌(CACC)模型。将BALB/c小鼠随机分为正常对照组、模型对照组和FLCWK组。给药结束后，用HE染色检测大鼠的病理状态。采用原位末端标记法和原位末端标记法观察肿瘤组织、肿瘤组织和结肠组织的细胞凋亡情况。采用免疫组织化学方法检测肿瘤组织、肿瘤组织和结肠组织中Caspase3、p-STAT3、Bcl2、Bax和P-gp的蛋白表达。结果：与5-FU单独作用相比，扶正胃康与5-FU合用可抑制HT-29细胞的活力，并诱导细胞周期阻滞和细胞凋亡。此外，与单独使用5-FU相比，FLCWK和5-FU联合应用可明显缩小肿瘤体积和重量，并通过降低p-STAT3和P-gp、增加Caspase 3蛋白表达而诱导肿瘤细胞凋亡。此外，结果显示，经FLCWK保护给药后，CACC小鼠的肿瘤数目和体积减少，p-STAT3和Bcl2水平下调，Bax和Caspase3表达上调。结论：FLCWK与5-FU通过抑制STAT3通路，下调P-gp表达，对结直肠癌有协同作用。此外，FLCWK通过抑制STAT3途径抑制CACC的发生。
Objective: To explore the effect of Feng-liao-chang-wei-kang (FLCWK) on acute and chronic gastroenteritis, synergistic effect on the growth inhibitory effect with 5-fluorouracil (5-FU) on colorectal cancer and its underlying mechanisms. Methods: In the in vitro study, HT-29 cells were divided into 5-FU alone, FLCWK alone and coadministration groups. The MTT assay was used to analyze the proliferation of HT-29 cells at 24 h. Flow cytometry was used to observe the apoptosis, cycle of colorectal cancer HT-29 cells at 24 h. In the in vivo experiment, The subcutaneous transplantation tumor model of colorectal cancer HT-29-Luc was established with nude mice. All mice were randomly divided into 5-FU alone, FLCWK alone and coadministration groups according to body weight. During administration, the Interactive Video Information System small animal live imaging system was used to monitor the growth of subcutaneous transplantation in nude mice. The model of colitis-associated colorectal cancer (CACC) was established with BALB/c mice. BALB/c mice were randomly divided into the normal control group, the model control group, and the FLCWK group. At the end of the administration, the pathological status was detected by HE staining. Cell apoptosis of tumor tissue tumor and colon tissues were observed by TUNEL staining and TUNEL green fluorescence. The protein expression of Caspase 3, p-STAT3, Bcl-2, Bax and P-gp in tumor tissues tumor and colon tissues were tested by using immunohistochemical assay. Results: FLCWK and 5-FU coadministration suppressed HT-29 cell viability and induced S phase arrest and apoptosis compared to treatment with 5-FU alone. Furthermore, compared to treatment with 5-FU alone, coadministration of FLCWK and 5-FU obviously reduced tumor volume and weight and induced apoptosis through decreasing p-STAT3 and P-gp and increasing Caspase 3 protein expression in a murine xenograft tumor model. Moreover, the result revealed decreased number and size of tumors following FLCWK protective administration, downregulated p-STAT3 and Bcl-2 levels and upregulated Bax and Caspase 3 expression in mice with CACC. Conclusions: FLCWK has synergistic effects with 5-FU on colorectal cancer by suppressing the STAT3 pathway and downregulating P-gp expression. Furthermore, FLCWK administration suppresses CACC tumorigenesis by inhibiting the STAT3 pathway.