P物质及其受体NK-1在结肠癌中的表达及作用
摘要
目的1.了解P物质(substance P, SP)及其受体神经激肽1(N K-1)在结肠癌组织及RKO细胞系中的表达特点,2.研究NK-1特异性激动剂[Sar9,Met(02)11] substance P (SMSP)以及特异性拮抗剂L-733,060对体外培养的人结肠癌细胞系RKO生长增殖的影响；3.探讨P物质及NK-1在结肠癌发展中的作用及临床意义。方法1.采用免疫组织化学染色研究P物质和NK-1在结肠癌组织(n=85)的表达及临床病理特点；同时采用免疫组化染色检测二者在结肠癌癌旁组织(n=26)以及正常粘膜(n=13)增生性息肉(n=22)和腺瘤(n=29)中的表达情况；2.采用免疫细胞化学染色检测二者在RKO细胞的表达特点；3.采用MTT比色法检测不同浓度的SMSP和L-733,060单独作用后RKO细胞活性的变化。结果①在结肠癌组织中P物质和NK-1表达阳性,呈巢状或弥漫分布。P物质阳性颗粒位于腺癌细胞胞浆,形态多呈圆形、椭圆形或不规则形；NK-1主要着色于细胞浆内,少数为于细胞膜。②二者在腺瘤组织、增生性息肉、癌旁组织和正常结肠组织也有表达,位于细胞浆内。③在RKO细胞系中P物质和N K-1呈阳性表达。P物质阳性表达主要位于细胞浆,而N K-1阳性表达主要位于细胞浆,部分位于细胞膜。④SMSP的浓度从10-10M到10-7M时它可以促进RKO细胞系的生长增殖,浓度为10-8M时其促增殖作用最明显,而到达10-6M时反而抑制RKO细胞系的增殖；L-733,060从10-10M到10-6M时能够减缓并抑制RKO细胞系的增殖,并且这种影响作用呈剂量依赖性。结论1.P物质与其受体NK-1在结肠癌组织中高度表达,提示神经内分泌与结肠癌的发生发展过程有关。2.究表明[Sar9,Met(02)11] substance P (SMSP)能够通过NK-1促进体外培养的RKO细胞系的增殖。3.L-733,60可以通过阻断NK-1在体外培养的结肠癌细胞系中可以发挥生长抑制作用,为NK-1将可能成为结肠癌新的治疗靶点提供了依据。
Objective 1.To study the expression of substance P (SP) and its receptor, neurokinin-1 (NK-1) in colon carcinomas and human colon cancer cell line RKO 2.Toevaluate the effect of potent selective NK-1 agonist [Sar9,Met(O2)11]substance P(SMSP) and selective antagonist L-733060 on human colon cancer cell line RKO in vitro.3. Toinvestigate the potential function of substance P and NK-1 in human colon cancer cellline RKO. Methods 1.The immunohistochemistry study was performed to detect theimmunolocation of substance P and neurokinin-1 in colon carcinomas (n=85). Several specimens were also selected to study as follows:normal colon specimens(n=13), adjacent specimens (n=22). hyperplastic polyps specimens (n=26), adenomas specimens (n=29).2. We carried out an in vitro immunocytochemical study to investigate the localization of substance P and NK-1 in RKO cells.3. various concentrations of SMSP (10-10M-10"6M) and L-733,060 (10-9M-10-5M) were applied alone in RKO cells. MTT assay were used to detect the cytoactivation. Results①We show here that colon carcinoma could co-express both substance P and NK-1.. The immunopositive substance P cells were distributed diffusely and the majority of SP labeling was localized within the cytoplasma of colon carcinoma, showed a diffuse or nest-like cytoplasmic staining. However, NK-1 could be observed in both plasma membrane and/or cytoplasma.②Substance p and receptor neurokinin-1 were also distributed in the cytoplasm in normal colorectal mucosal specimens, hyperplastic polyp, colon adenoma and adjacent specimens on cytoplasm.③. In RKO cells, we found immunoreactive substance P was mainly presented on cytoplasm and NK-1 on both membrane and plasma.④.At a concentration of 10-8M SMSP exerted maximum proliferation action and L-733,060 (10-10-10-6M) inhibited cell growth in a dose dependent manner. Conclusion 1.Given that both colon carcinoma tissues and RKO cell line bear over expression of substance P and NK-1, it is suggested that neuroendocrine mechanisms participate the development of colon carcinoma.2. L-733,060 could blunt cell growth via NK-1 in vitro.3. Substance P may stimulate cell proliferation through NK-1 in vivo; NK-1 may serve as a critical gate to regulate substance P related cell proliferation and a new target for therapy.
Objective 1.To study the expression of substance P (SP) and its receptor, neurokinin-1 (NK-1) in colon carcinomas and human colon cancer cell line RKO 2.Toevaluate the effect of potent selective NK-1 agonist [Sar9,Met(O2)11]substance P(SMSP) and selective antagonist L-733060 on human colon cancer cell line RKO in vitro.3. Toinvestigate the potential function of substance P and NK-1 in human colon cancer cellline RKO. Methods 1.The immunohistochemistry study was performed to detect theimmunolocation of substance P and neurokinin-1 in colon carcinomas (n=85). Several specimens were also selected to study as follows:normal colon specimens(n=13), adjacent specimens (n=22). hyperplastic polyps specimens (n=26), adenomas specimens (n=29).2. We carried out an in vitro immunocytochemical study to investigate the localization of substance P and NK-1 in RKO cells.3. various concentrations of SMSP (10-10M-10"6M) and L-733,060 (10-9M-10-5M) were applied alone in RKO cells. MTT assay were used to detect the cytoactivation. Results①We show here that colon carcinoma could co-express both substance P and NK-1.. The immunopositive substance P cells were distributed diffusely and the majority of SP labeling was localized within the cytoplasma of colon carcinoma, showed a diffuse or nest-like cytoplasmic staining. However, NK-1 could be observed in both plasma membrane and/or cytoplasma.②Substance p and receptor neurokinin-1 were also distributed in the cytoplasm in normal colorectal mucosal specimens, hyperplastic polyp, colon adenoma and adjacent specimens on cytoplasm.③. In RKO cells, we found immunoreactive substance P was mainly presented on cytoplasm and NK-1 on both membrane and plasma.④.At a concentration of 10-8M SMSP exerted maximum proliferation action and L-733,060 (10-10-10-6M) inhibited cell growth in a dose dependent manner. Conclusion 1.Given that both colon carcinoma tissues and RKO cell line bear over expression of substance P and NK-1, it is suggested that neuroendocrine mechanisms participate the development of colon carcinoma.2. L-733,060 could blunt cell growth via NK-1 in vitro.3. Substance P may stimulate cell proliferation through NK-1 in vivo; NK-1 may serve as a critical gate to regulate substance P related cell proliferation and a new target for therapy.
引文
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