葡萄籽多酚对人乳腺癌细胞MCF-7/ADR在裸鼠体内的多药耐药逆转作用

目的　研究葡萄籽多酚 (GSP)对人乳腺癌耐阿霉素细胞MCF 7/ADR的体内多药耐药逆转作用。方法　采用人乳腺癌裸鼠移植瘤模型研究GSP对肿瘤多药耐药的体内逆转作用 ;采用流式细胞术测定不同用药P 糖蛋白 (Pgp)表达变化及肿瘤细胞凋亡率变化。 结果　体内裸鼠抑瘤实验显示GSP有一定抑瘤作用 ,抑制率为 18 35 % ,联合应用阿霉素 (ADR)可显著抑制肿瘤生长 ,2 0mg/kgGSP可有效逆转MCF 7/ADR细胞的耐药性 ,抑瘤率为 5 4 6 4 %。流式细胞术结果显示应用GSP后肿瘤细胞Pgp表达显著降低 ( 32 0 3± 2 0 9) ,与对照组 ( 5 5 13± 2 12 )相比差异有显著意义 (P <0 0 5 )。平均凋亡率为 15 12 %± 1 0 4 % ,显著高于对照组 9 0 7%± 0 4 3% (P <0 0 5 )。结论　GSP能在体内逆转MCF 7/ADR细胞的耐药性 ,其机制可能是通过抑制Pgp表达 ,并可能通过诱导肿瘤细胞凋亡来起作用     

熊果酸对MCF-7乳腺癌细胞生长的影响

目的 观察熊果酸对MCF-7乳腺癌细胞增殖、凋亡、细胞侵袭及裸鼠移植瘤生长的影响.方法 将1、10、100 μmol/L的熊果酸分别作用于乳腺癌MCF-7细胞12、24、48 h,噻唑蓝(MTT)比色法检测细胞活力变化及生长抑制率,流式细胞术及Transwell小室法检测熊果酸作用48h时MCF-7细胞周期、细胞凋亡率及细胞侵袭力.将乳腺癌MCF-7细胞接种于裸鼠,成瘤后分为生理盐水对照组、熊果酸低剂量组(每日1 mg/kg)、中剂量组(每日5 mg/kg)和高剂量组(每日25 mg/kg),检测5、10、15 d裸鼠移植瘤体积、肿瘤生长抑制率及15 d时肝肾功能、血常规变化.结果 随熊果酸浓度增加及作用时间延长,MCF-7细胞生长及凋亡发生受到显著影响,100 μmol/L熊果酸作用48 h时,细胞生长抑制率为46.0%,生长周期阻滞于G0/G1期,细胞凋亡率为(16.48±2.46)%,细胞侵袭力显著下降.熊果酸组裸鼠移植瘤体积显著小于对照组,15 d时熊果酸高剂量组肿瘤体积为(323.5±33.5)mm3生长抑制率为50.9%.各组肝肾功能和血常规无明显变化.结论 熊果酸可引起体外乳腺癌McF-7细胞增殖抑制、细胞凋亡率增加及细胞侵袭力下降,可显著抑制裸鼠乳腺癌移植瘤生长.     

Establishment of a human gastrinoma in nude mice

We report the first establishment and characterization of functioning gastrinoma from a human being transplanted into nude mice. Tissue was obtained at operation from a gastrinoma liver metastasis from a patient with the Zollinger-Ellison syndrome. The tumor was implanted subcutaneously in five athymic nude mice. Serum gastrin was measured by means of radioimmunoassay in specimens of mouse blood taken before and 5 minutes after intraperitoneal injection of secretin (100 micrograms/kg). In a second experiment serum gastrin was measured 30 minutes after injection of somatostatin analogue, SMS 201-995 (300 micrograms/kg). Studies were also done in 10 control mice. At passage, the fundus of each tumor-bearing mouse was weighed and examined microscopically. The gastrinoma (tumor line, PT) has been maintained for 34 months through four passages with a tumor doubling time of 37 to 45 days. The histology is similar to the original tumor. Immunocytochemistry showed that PT contained gastrin. In two mice metastasis developed 9 months after implantation. Gastrin levels in mice bearing PT have ranged from 216 to 12,000 pg/ml. Gastrin levels of control mice ranged from 0 to 63 pg/ml. Secretin increased gastrin levels in three of five mice tested and decreased gastrin levels in two mice. Repeat secretin tests showed identical results. SMS 201-995 decreased gastrin levels from basal values. Fundic weight of mice bearing PT (397 +/- 93 mg) was significantly greater than control fundic weight (180 +/- 26 mg). Gastrinomas growing in nude mice produce physiologically active gastrin as shown by elevated serum gastrin levels and by hyperplasia of the stomach. Two distinct subpopulations of gastrinoma cells respond differently to secretin. This model should provide important information on mechanisms of growth control and on gastrin release by gastrinomas in human beings.     

The effects of estrogen on human breast carcinomas serially transplanted into nude mice

The effect and mechanisms of 17 beta-estradiol (E2) on breast cancer cells were studied in vivo and in vitro, using 5 human breast carcinomas serially transplanted into nude mice. These carcinoma strains consisted of 4 estrogen receptor (ER) positive tumors and 1 ER negative tumor. Mice bearing these tumors were treated with an intramuscular injection of E2 at a dosage of 50 mg/kg and the tumor doubling time (Td) was calculated in days. The tumor growth was significantly stimulated by E2 in 3 out of the 4 ER positive tumors, the Td of the E2 treated groups being 17.6 days for MCF-7 (control: -17.8 days), 12.8 days for R-27 (control: -12.5 days approximately 14.5 days) and 10.4 days for Br-10 (control: 14.5 days), however, in the T-61 tumor, the growth was inhibited by E2 in a dose dependent manner. In the case of the ER-negative MX-1 tumor, the tumor cell growth was not affected by E2. Discrepancies between the effects of E2 on ER-positive tumors were further analyzed by examining the steroid hormone receptor status and conducting in vitro growth studies. In vitro clonogenic cell assay reproduced the antitumor activity of E2, indicating that E2 directly inhibits part of the cell growth of T-61 tumors. The above results suggest that this experimental system provides a useful tool for analyzing the mechanism of estrogen in breast cancer and that the clonogenic assay using ER positive specimens can help to identify breast cancers sensitive to estrogen therapy.     

低分子肝素对种植性乳腺癌生长和转移的抑制作用

目的 观察低分子肝素在种植性乳腺癌动物模型中对肿瘤生长和转移的抑制作用.方法 制作120例MCF-7乳腺癌细胞移植瘤裸鼠模型,将其随机分为低分子肝素组、生理盐水组、化疗组、内分泌治疗组,每组30只;观察裸鼠一般情况及移植瘤的牛长变化,28 d后统一脱颈椎处死裸鼠,切取移植瘤标本进行常规镜检及应用免疫组织化学检测瘤组织内血管内皮生长因子(VEGF)和微血管密度(MVD)的变化.结果 实验4周后,低分子肝素组、化疗组、内分泌治疗组不仅在移植瘤体积、胸壁浸润及淋巴转移等方面明显优于生理盐水组,其VEGF、MVD的表达亦低于生理盐水组,差异有统计学意义(P<0.01);其中尤以低分子肝素组中VEGF、MVD的表达更低,但与化疗组、内分泌治疗组间对比差异并无统计学意义(P>0.01).结论 低分子肝素在裸鼠MCF-7移植瘤模型中可以通过抑制肿瘤血管形成而抑制移植瘤的生长及转移.     

~(131)Ⅰ-17-丙烯胺基-17-去甲氧基格尔德霉素对荷MCF-7乳腺癌模型的抑瘤作用

目的 观察~(131)Ⅰ-17-丙烯胺基-17-去甲氧基格尔德霉素(17-AAG)对MCF-7乳腺癌荷瘤裸鼠模型肿瘤生长的抑制作用.方法 采用过氧化氢标记法制备~(131)Ⅰ-17-AAG;将30只荷瘤裸鼠随机分成3组:~(131)Ⅰ-17-AAG治疗组,二甲基亚砜(DMSO)对照组和单纯Na~(131)Ⅰ治疗组.尾静脉注射相应试剂后,观察28 d,比较肿瘤的体积,计算抑瘤率;Western blot检测肿瘤组织Akt2蛋白表达情况;观察肿瘤组织病理变化;TUNEL法检测肿瘤组织细胞凋亡.结果 给药28 d,肿瘤体积依序分别为(63.75±8.62)、(96.79±14.75)、(83.12±10.89)mm~3;~(131)Ⅰ-17-从G组与DMSO对照组和~(131)Ⅰ组两组间比较,差异有统计学意义(F=23.13,20.58,P＜0.01);DMSO对照组和~(131)Ⅰ组比较,差异无统计学意义(F=3.43,P＞0.05);~(131)Ⅰ-17-AAG治疗组Akt2蛋白表达较对照组明显降低.结论 ~(131)Ⅰ-17-AAG能有效抑制裸鼠MCF-7乳腺癌的生长,对治疗人MCF-7乳腺癌有较好实践意义.     

PGL3-DF3-DTA在DF3阳性人乳腺癌细胞移植瘤中的表达和作用

目的:探讨含人乳癌DF3/MUC1启动子转录调控序列的DTA重组表达载体PGL3-DF3-DTA对乳腺癌DF3阳性癌细胞的选择性表达和杀伤作用。 方法:将乳腺癌的两种细胞株MCF-7和MDA-MB-231分别接种于裸鼠背侧皮下，7 d后开始用重组的质粒进行活体内瘤注射治疗。肿瘤接种后第29天脱颈椎处死裸鼠，测量移植瘤的体积和质量;并采用逆转录-聚合酶链反应法（RT-PCR）检测裸鼠移植瘤内DTA的表达情况。 结果:重组表达载体PGL3-DF3-DTA在MCF-7细胞株移植瘤中表达，明显抑制肿瘤生长。结论:重组表达载体PGL3-DF3-DTA对乳腺癌DF3阳性的癌细胞起到了选择性表达和杀伤作用。     

血管内皮因子-C_短发夹RNA靶向微泡联合超声辐照对裸鼠乳腺癌的抑制效应

目的探讨血管内皮生长因子-C_短发夹RNA（VEGF-C_shRNA）靶向微泡联合超声辐照对乳腺肿瘤生长的抑制作用。方法对32只雌性BALB/c裸鼠原位接种MCF-7人乳腺癌肿瘤组织。待移植瘤成瘤后,随机分为4组,G1组为空白对照,G2组采用VEGF-C_shRNA靶向微泡联合辐照,G3组为空白微泡＋辐照,G4组为VEGF-C_shRNA静脉治疗。VEGF-C_shRNA靶向微泡治疗中,采用眼球后静脉注射150μg/kg两次,每次注射微泡后采用超声定位肿瘤后对微泡进行多次辐照。观察各组乳腺癌生长的情况。结果 G2组肿瘤增长幅度明显小于其他组,尤其是在治疗后第3、7、17天其平均增殖率与G1组差异有统计学意义（P均〈0.05）,G2组与G3组比较,第3、7、10、13、17及20天的差异均有统计学意义（P均〈0.05）,G2组与G4组第7、13天以及17天的差异有统计学意义（P〈0.05）。结论 VEGF-C_shRNA靶向微泡联合辐照可以抑制裸鼠乳腺癌的生长。     

Survivin反义寡核苷酸对乳腺癌荷瘤裸鼠的抑瘤作用研究

目的探讨survivin反义寡核苷酸（ASODN）对乳腺癌荷瘤裸鼠的抑瘤作用。方法30只裸鼠建立人乳腺癌MCF-7细胞移植瘤动物模型。成瘤后动物随机分3组，每组10只。分别于瘤周及瘤体注射阳离子脂质体（1ipofectin，Lip），ASODN／Lip及NODN／Lip，每5天1次，共3次。观察肿瘤抑制率、肿瘤体积和裸鼠体重的变化。用TUNEL法，透射电镜观察体内瘤体的细胞调亡情况；用Western—blot检测各组肿瘤的survivin蛋白表达情况。结果成功建立了裸鼠皮下移植瘤模型。ASODN／Lip治疗组的肿瘤体积在治疗期内减少，抑瘤率达70．10％；而NODN／Lip治疗组和Lip对照组肿瘤体积增加。各组裸鼠体重无明显变化。ASODN／Lip组细胞凋亡率为38．6％明显高于其他两组，差异有显著性（P〈0．05）。ASODN／Lip组肿瘤的survivin蛋白表达明显降低。结论survivin反义寡核苷酸可有效地抑制人乳腺癌裸鼠皮下肿瘤的生长速度，并促进诱导肿瘤细胞的凋亡。     

维生素E琥珀酸酯对乳腺癌荷瘤裸鼠的抑瘤作用

目的 检测维生素E琥珀酸酯（VES）对裸鼠荷乳腺癌MCF-7细胞的抑制作用。方法 裸鼠皮下接种MCF-7乳腺癌细胞建立荷瘤裸鼠模型。以150mg／kg（体重）剂量的VES治疗模型鼠共5周。处死动物后测量肿瘤大小。以流式细胞仪检测细胞周期变化和细胞表面Fas和FasL的表达；以免疫组化法检测肿瘤组织Fas和FasL的表达，并以TUNEL法检测细胞凋亡指数。结果 VES对荷乳腺癌裸鼠具有显著的增殖抑制作用。细胞周期分析显示，VES冶疗后肿瘤细胞表现为G0／G1期阻滞，肿瘤组织和细胞表面的Fas和FasL均出现上调，同时细胞的凋亡指数升高。结论 VES对于MCF-7乳腺癌荷瘤裸鼠具有强效的抑制作用，其机制与上调肿瘤细胞Fas／FasL表达，促进细胞凋亡有关。     

表皮生长因子受体抑制剂AG1478对乳腺癌裸鼠移植瘤的生长影响

目的 观察表皮生长因子受体抑制剂AG1478和内分泌治疗联合应用对乳腺癌荷瘤裸鼠移植瘤生长的影响.方法 应用MCF-7乳腺癌细胞建立裸鼠动物模型,当肿瘤体积在100～200 mm3时,按肿瘤体积大小将裸鼠随机分成溶剂对照组、AG1478组、三苯氧胺(TAM)组、AG1478+TAM组,分别给予空白溶剂、AG1478腹腔注射、TAM灌胃、AG1478腹腔注射和TAM灌胃.同时给药6周,动态观察移植瘤生长,用药结束后2d处死裸鼠,取肿瘤称重、计算肿瘤体积(V=长径×短径2×π/6)、抑瘤率([(V对照组-V实验组)/V对照组]×100%).结果 各组裸鼠体重和肿瘤体积在治疗前具有均衡性.用药期间,溶剂对照组肿瘤生长最快,AGl478组次之,TAM组肿瘤生长较缓慢,而AGl478+TAM组肿瘤有缩小趋势.用药结束后,各组的抑瘤率分别为AG1478组30.4%,TAM组62%,AG1478+TAM组84.8%,与对照组比较差异有统计学意义(P<0.05).结论 AG1478对乳腺癌裸鼠移植瘤具有抑制作用,也可以加强三苯氧胺的抑瘤效果,两者有明显协同作用.     

~（125）I在乳腺肿瘤中对内皮抑素的作用及机制研究

目的：研究125I粒子对乳腺肿瘤组织内皮抑素（ES）表达水平的影响,探讨125I粒子对抑肿瘤血管生长基因的作用及其分子生物学机制。方法：建立人类乳腺癌MCF-7细胞株的裸鼠皮下移植瘤模型,将荷瘤鼠分两组：对照组,植入空载粒子;实验组：植入125I粒子。粒子植入后当对照组瘤体平均长径约为15～20mm时,处死荷瘤小鼠,标本分别冻存和固定,用半定量RT-PCR、Western blotting印迹及免疫组化染色方法检测ES的mRNA及其蛋白表达水平。结果：实验组中肿瘤组织及癌旁组织的ES的mRNA及其蛋白表达明显升高,与对照组相比,差异有显著性意义（P〈0.01）。两组肿瘤中正常组织ES的mRNA及其蛋白的表达变化不明显,无显著性差异（P〉0.05）。结论：125I粒子促进乳腺肿瘤组织抑肿瘤血管生长因子ESmRNA及其蛋白水平的表达。     

瘦素对人乳腺癌裸鼠移植瘤雌激素受体α、βmRNA的调控作用

目的通过荷人乳腺癌裸鼠模型来进行在体研究外源性人类瘦素对移植瘤组织内雌激素受体(ER)a、β mRNA的调控作用.方法应用人乳腺癌MCF-7细胞制备荷人乳腺癌裸鼠模型,随机分成瘦素实验组(n=30)及0.9%的氯化钠溶液对照组(n=30).实验组采用瘤周皮下注射人重组瘦素连续15 d,对照组给予皮下注射相同剂量0.9%的氯化钠溶液.实时荧光PCR法扩增移植瘤组织内ERα、ERβ mRNA并进行相对定量分析.结果成功建立荷人乳腺癌裸鼠模型,并进行了瘤周皮下注射人类瘦素干预.ERα mRNA表达量在瘦素组高于0.9%的氯化钠溶液组(P＜0.01),ERβmRNA表达量在瘦素组低于0.9%的氯化钠溶液组(P＜0.01).结论通过瘤周皮下注射人类瘦素来干预荷人乳腺癌裸鼠是安全的.ERα与ERβ都可作为人类瘦素的作用靶点.外源性人类瘦素可以上调人乳腺癌裸鼠异种移植瘤内ERαmRNA的表达,下调ERβ mRNA的表达.

Abstract：

Objective To investigate the different effect of exogenous leptin on estrogen receptor α,β mRNA in human breast tumor tissue in nude mice xenograft models. Methods We made nude mice xenograft models of MCF-7 human breast cancer cells cultured in vitro, then divided them into experimental group of]eptin( n = 30)and control group of normal saline( n = 30)randomly. The models of experimental group were injected subcutaneously the recombinant human leptin for 15 consecutive days, the models of control group were injected subcutaneously the same dose of normal saline. A real- time quantitative RT- PCR assay was developed to quantify the expression of estrogen receptor α, β mRNA in tumor tissue, using the relative quantitative analysis. Results The leptin-intervened nude mice xenograft models were safely established. The relative quantitation of estrogen receptor α mRNA was significantly higher in the leptin group than in the normal saline group ( P ＜ 0.01 ), the relative quantitation of estrogen receptor β mRNA was significantly lower in the leptin group than in the normal saline group ( P ＜ 0. 01 ). Conclusion The nude mice xenograft models can be safely intervened with human leptin by subcutaneous injection around tumor.Estrogen receptor is one of the targets of leptin in the progress of breast cancer. Exogenous human leptin can up- regulate the expression of estrogen receptor α and down- regulate the expression of the estrogen receptor βin nude mice xenograft models of human breast tumor.     

~(125)I粒子抑制乳腺癌细胞bFGF表达的实验研究

目的:探讨125I粒子对乳腺癌细胞中碱性成纤维细胞因子(bFGF)表达的影响及其在抑制肿瘤细胞增殖方面的作用机制。方法:建立人乳腺癌细胞株MCF-7裸鼠皮下移植瘤模型,根据处死时间,随机分为8组,包括D7、D14、D21、D28组(对照组)及S7、S14、S21、S28组(实验组),每组6只,对照组植入空白粒子(0 mCi),实验组植入125I粒子(0.4 mCi)。观察粒子植入后瘤体生长情况,粒子植入后第7、14、21、28天分别处死各组荷瘤小鼠。半定量RT-PCR、免疫组织化学染色方法检测bFGF mRNA及其蛋白的表达。结果:植入125I粒子后,实验组肿瘤生长缓慢,肿瘤抑制率为53.27%。粒子植入第28天,与对照组相比,实验组肿瘤组织的bFGF mRNA及蛋白表达明显降低,差异有统计学意义(χ2=45.788,P<0.01)。结论:125I粒子抑制bFGF mRNA和蛋白的表达是其治疗乳腺癌增殖的分子生物学机制之一。     

Inhibition of growth of two human pancreatic adenocarcinomas in vivo by somatostatin analog SMS 201-995

Somatostatin inhibits hormone secretion from gastrointestinal endocrine tumors. The purpose of this study was to determine whether SMS 201-995, a long-acting analog, would inhibit the growth of pancreatic adenocarcinomas. Two human pancreatic cancers grown in nude mice were studied: SKI, which has cholecystokinin receptors, and CAV, which does not. Tumors were implanted in groups of six mice each. Treatment groups received SMS 201-995 (100 micrograms/kg three times daily) by intraperitoneal injections and control animals received saline solution. Tumor area was measured twice weekly. After 7 weeks, the tumors and mouse pancreases were excised, weighed, and analyzed for protein and RNA and DNA content. In a second set of experiments, treatment was begun 21 days after transplantation. Mean body weights between groups were not different in any experiment. With treatment beginning on the day of transplantation, the tumor areas of SKI and CAV cancers were reduced by the third and fifth weeks of treatment, respectively. Tumor doubling times were prolonged with treatment in both SKI tumors (5 days) and CAV tumors (6 days). In the SKI treatment groups, tumor weight (52 percent), RNA content (72 percent), and DNA content (60 percent) were decreased at sacrifice compared with those of the control groups. In the CAV treatment group, the mean tumor weight (55 percent) and protein (48 percent), RNA (67 percent) and DNA contents (60 percent) were decreased compared with the CAV control group. Tumor growth of SKI and CAV cancers was also inhibited when treatment was delayed 21 days after transplantation. We conclude that these effects are not mediated by inhibition of cholecystokinin, as seen by similar inhibitory effects on both tumors. Treatment with SMS 201-995 may be an effective hormonal therapy in patients with pancreatic cancers.     

Experimental and clinical study on flow cytometric DNA analysis of human breast carcinoma

Flow cytometric DNA analysis was performed on four human breast carcinoma xenografts serially transplanted into nude mice (MX-1, T-61, R-27 and MCF-7) together with 31 surgical specimens of breast carcinoma. Mechanically dissociated tumor cells were stained with propidium iodide and histograms were obtained by counting at least 2 x 10(4) cells using EPICS-V flow cytometer. Tumor ploidy was expressed as DNA Index using internal standard of chicken red blood cells and the percentage of cells in the S phase of cell cycle was determined by Bagwell's program. All of four xenografts and 23 of 31 clinical specimens showed non-diploid pattern. Statistically significant correlation was observed between %S and tumor doubling time of human tumor xenografts, viewed rapid growing tumor revealed high %S. In clinical cases, statistically significant correlation was present between %S and histological grade and the state of hormone receptors. Histological grade III tumors had a significantly higher %S than that of histological grade I tumors. ER negative tumors showed a significantly higher mean %S than that of ER positive tumors. Similarly, PgR negative tumors possessed a significantly higher mean %S than that of PgR positive tumors. However, no significant correlation was found between ploidy pattern and clinicopathological parameters. It was concluded that flow cytometric %S might be useful to estimate the biological malignancy of human breast carcinomas.     

The effects of estrogen on human breast carcinomas serially transplanted into nude mice

The effect and mechanisms of 17β-estradiol (E₂) on breast cancer cells were studiedin vivo andin vitro, using 5 human breast carcinomas serially transplanted into nude mice. These carcinoma strains consisted of 4 estrogen receptor (ER) positive tumors and 1 ER negative tumor. Mice bearing these tumors were treated with an intramuscular injection of E₂ at a dosage of 50 mg/kg and the tumor doubling time (Td) was calculated in days. The tumor growth was significantly stimulated by E₂ in 3 out of the 4 ER positive tumors, the Td of the E₂ treated groups being 17.6 days for MCF-7 (control: −17.8 days), 12.8 days for R-27 (control: −12.5 days∼14.5 days) and 10.4 days for Br-10 (control: 14.5 days), however, in the T-61 tumor, the growth was inhibited by E₂ in a dose dependent manner. In the case of the ER-negative MX-1 tumor, the tumor cell growth was not affected by E₂. Discrepancies between the effects of E₂ on ER-positive tumors were further analyzed by examining the steroid hormone receptor status and conductingin vitro growth studies.In vitro clonogenic cell assay reproduced the antitumor activity of E₂, indicating that E₂ directly inhibits part of the cell growth of T-61 tumors. The above results suggest that this experimental system provides a useful tool for analyzing the mechanism of estrogen in breast cancer and that the clonogenic assay using ER positive specimens can help to identify breast cancers sensitive to estrogen therapy.     

Gastrin-releasing peptide-, calcitonin gene-related peptide-, and calcitonin-like immunoreactivity in human breast cyst fluid and gastrin-releasing peptide-like immunoreactivity in human breast carcinoma cell lines

To assess the role of growth factors in proliferative disorders of the breast, we assayed breast cyst fluid from 70 patients for calcitonin-related peptides. Cyst fluids (5.4 +/- 6.6 ml) (mean +/- SD) (n = 70) contained 10,499 +/- 8272 pg/ml of gastrin-releasing peptide (GRP)-like immunoreactivity in 66 of 70 samples. Calcitonin gene-related peptide (CGRP)-like immunoreactivity was found in 64 of 64 samples tested (3842 +/- 2048 pg/ml). Calcitonin-like immunoreactivity was detected in 47 of 69 samples (185 +/- 106 pg/ml). Significant correlations were found for GRP versus volume, CGRP, and calcitonin, for calcitonin versus volume and CGRP, and for CGRP versus volume. Extracts of two human breast carcinoma cell lines (MCF-7 and BT-20) contained measurable GRP-like immunoreactivity. We conclude that GRP-, CGRP-, and calcitonin-like immunoreactivities are present in human breast cyst fluid and that GRP-like immunoreactivity is present in two established human breast carcinoma cell lines. High concentrations of GRP-like immunoreactivity in both breast cyst fluid and breast carcinoma tissue, taken together with the known mitogenic and trophic activities of this peptide, support the hypothesis that GRP may be an important factor in human breast disease.     

内皮抑素对乳腺癌MCF-7细胞裸鼠移植瘤的抑制作用

目的 观察内皮抑素对乳腺癌裸鼠皮下移植瘤的影响,探讨内皮抑素用于乳腺癌治疗的应用前景.方法 MTT法测定内皮抑素对MCF-7细胞生长的抑制率.构建乳腺癌细胞MCF-7裸鼠皮下移植瘤模型,瘤体周边注射内皮抑素,观察其对乳腺癌细胞的抑制作用.结果 10μg/mL和15 μg/mL浓度的内皮抑素能有效抑制MCF-7细胞生长(P<0.05).皮下注射内皮抑素后,移植瘤的瘤重和瘤体积及肿瘤微血管密度均较对照组下降(P<0.05).结论 内皮抑素具有良好的生物学活性,通过抑制血管生成及直接抑制肿瘤细胞生长而发挥抗乳腺癌的作用.