6-formylindolo [3, 2-b] carbazole inhibits proliferation in colon cancer cells by down-regulating keratinocyte growth factor receptor

殷久恒; 韩宾; 蒲爱民; 盛百伐; 于敏; 孙力华; 王启萌; 杨坤秋; 杨桦

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6-formylindolo [3, 2-b] carbazole inhibits proliferation in colon cancer cells by down-regulating keratinocyte growth factor receptor

更新时间：2026-01-09

- 6-formylindolo [3, 2-b] carbazole inhibits proliferation in colon cancer cells by down-regulating keratinocyte growth factor receptor
- Journal of Army Medical University Vol. 37, Issue 23, Pages: 2315-2319(2015)
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  CLC： R73-361;R730.23;R735.35
- Published：2015
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殷久恒,韩宾,蒲爱民,盛百伐,于敏,孙力华,王启萌,杨坤秋,杨桦.6甲酰基吲哚并[3,2-b]咔唑通过下调角质细胞生长因子受体抑制结肠癌细胞增殖[J].陆军军医大学学报(原第三军医大学学报),2015,37(23):2315-2319.

　Yin Jiuheng,Han Bin,Pu Aimin,Sheng Baifa,Yu Min,Sun Lihua,Wang Qimeng,Yang Kunqiu,Yang Hua.6-formylindolo [3, 2-b] carbazole inhibits proliferation in colon cancer cells by down-regulating keratinocyte growth factor receptor[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(23):2315-2319.
殷久恒,韩宾,蒲爱民,盛百伐,于敏,孙力华,王启萌,杨坤秋,杨桦.6甲酰基吲哚并[3,2-b]咔唑通过下调角质细胞生长因子受体抑制结肠癌细胞增殖[J].陆军军医大学学报(原第三军医大学学报),2015,37(23):2315-2319. DOI：

　Yin Jiuheng,Han Bin,Pu Aimin,Sheng Baifa,Yu Min,Sun Lihua,Wang Qimeng,Yang Kunqiu,Yang Hua.6-formylindolo [3, 2-b] carbazole inhibits proliferation in colon cancer cells by down-regulating keratinocyte growth factor receptor[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(23):2315-2319. DOI：

摘要

目的研究芳香烃受体(aryl hydrocarbon receptor

AhR)及其配体6甲酰基吲哚并[3

2-b]咔唑（6-formylindolo [3

2-b] carbazole，FICZ）对结直肠癌上皮细胞表面角质细胞生长因子受体（keratinocyte growth factor receptor，KGFR）的调控和对细胞增殖的影响。方法选用免疫组化和荧光定量PCR技术分别检测KGFR在结直肠正常组织和相应癌组织中的表达和定位，免疫荧光观察AhR在两种结肠癌细胞株（LoVo，Caco-2细胞株）中的分布，使用蛋白免疫印迹和荧光定量PCR 检测AhR、细胞色素P4501A1（CYP1A1）、KGFR在FICZ处理组和对照组中的表达差异，使用细胞计数板分别检测对照组，KGF处理组

KGF+FICZ处理组和FICZ处理组各组的细胞数。结果 12个结直肠癌临床样本中有11个患者样品中KGF高表达，8个患者样品中KGFR显著增高且KGFR主要高表达于上皮细胞。体外实验发现，FICZ处理后的LoVo细胞中KGFR的蛋白水平和mRNA水平分别降低了50%和58.8%。在Caco2细胞中分别降低了52.6%和62.5%。这种调节过程能被AhR抑制剂CH223191阻断。同时，在两种结肠癌细胞系中，FICZ能够降低KGF对癌细胞的增殖作用（LoVo:34%;Caco-2:37%）。结论 AhR通过下调KGFR的表达，抑制KGF对癌细胞的增殖效应。

Abstract

Objective To determine the regulative effect of aryl hydrocarbon receptor (AhR) and its ligand

6-formylindolo [3

2-b] carbazole (FICZ)

in the expression of keratinocyte growth factor receptor (KGFR) and proliferation in colorectal cancer epithelial cells. Methods The expression and location of KGFR were detected in the normal tissues and colorectal cancer tissues by immunohistochemical staining and real-time PCR. Immunofluorescence assay was used to observed the location of AhR in LoVo and Caco-2 cell lines. The expression levels of AhR

CYP1A1 and KGFR were detected by Western blotting and real-time PCR in the FICZ treated cells and control cells. Cell proliferation was measured by counting the cell number among the normal

KGF treated

KGF+FICZ treated and FICZ treated cells

respectively. Results KGF was highly expressed in the 11 specimens from the 12 cancer cases

and KGFR was strongly expressed in the 8 specimens of 12 cases and was located mainly on the intestinal epithelial cells. In vitro study found that FICZ treatment resulted in 50% and 58.8% respectively decreases in the expression of KGFR at protein and mRNA levels in LoVo cells

and 52.6% and 62.5% respectively in Caco-2 cells. However

AhR inhibitor CH223191 could block this down-regulated expression of KGFR. Furthermore

FICZ could decrease the KGF-induced cell proliferation in LoVo (34%) and Caco-2 cells (37%). Conclusion AhR inhibits the proliferation of colon cancer cells induced by KGF through down-regulating the expression of KGFR.

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