砷致HeLa细胞基因组DNA损伤的特点

目的 观察砷致HeLa细胞基因组DNA损伤的特点。方法 在彗星实验中应用彗星图像分析系统（KIAS）技术。结果 砷剂量与DNA拖尾细胞比率之间存在明确的剂量效应递增关系，而且给药各组与阴性对照组细胞在拖尾形态上存在较大差异。结论 砷致HeLa细胞基因组DNA的损伤表现出一定的特异性。     

慢性砷暴露对雌鼠卵巢发育的影响

目的通过观察慢性砷暴露昆明种雌鼠卵巢的形态学改变和血清激素雌二醇、孕酮含量变化,探讨砷发挥雌激素效应对卵巢发育的影响及内分泌干扰机理。方法选择暴露于不同浓度As2O3(0、0.05、0.10、0.20、0.40μg/ml)饮水20周的昆明种雌鼠为研究对象,通过HE染色,光镜观察卵巢组织形态变化,采用放射免疫法测定血清激素雌二醇与孕酮含量。结果随着As2O3浓度增加,各剂量组卵巢的卵泡数均有减少趋势,发育异常。血清雌二醇和孕酮含量均有变化。结论慢性砷暴露可造成卵巢组织形态学改变,扰乱血清激素水平,砷具有雌激素效应。     

砷的生殖发育毒性及雌激素效应研究进展

砷作为一种环境毒物,对健康的损害是全身性的、多系统的.人暴露于无机砷,可引起膀胱癌、肺癌、皮肤癌、肝癌、肾癌以及许多其他非癌毒性效应,如皮肤损害、心脑血管疾病、糖尿病、神经系统效应及生殖毒性效应等.     

雌激素膜快速效应对人成骨样细胞MG63 OPG mRNA快速表达水平的影响

目的 探讨17β-雌二醇(E2)膜快速效应对人成骨样细胞MG63的OPG mRNA快速表达水平影响.方法 采用RT-PCR法分析经E2快速作用后的MG63细胞中OPG mRNA的表达水平.结果 E2膜快速效应能诱导人成骨细胞MG63 OPG mRNA表达水平出现一个快速增高现象,其表达高峰时间为E2作用后的10 min左右,而且这一现象能被G蛋白藕联抑制苏拉明所抑制.结论 而E2诱导的人成骨样细胞MG63中OPG mRNA表达水平的快速增高,可能与雌激素启动了雌激素膜受体介导的G蛋白藕联受体调节的磷脂酶C/腺苷酸环化酶通路有关.     

As2O3与NaAsO2抑制HeLa细胞生长的研究

目的探讨As2O3和NaAsO2两种砷剂对HeLa细胞的抑制作用.方法培养HeLa细胞,使细胞悬液浓度为105个/mL,用四甲基偶氮唑蓝还原反应(MTT法),倒置显微镜观察两种砷剂对HeLa细胞的作用后细胞形态的变化.结果两种砷剂As2O3和NaAsO2对HeLa细胞均有抑制作用,随着药物浓度的增加,HeLa细胞存活率逐渐下降并存在剂量反应关系,显微镜下观察,三角形的活细胞逐渐减少而圆形的死亡细胞逐渐增加,As2O3的作用比NaAsO2作用强,对照组均未见上述变化. 结论两种砷剂对HeLa细胞均有抑制作用,As2O3的作用比NaAsO2作用强.     

葛根素对HeLa细胞生长的抑制作用机制

目的探讨葛根素对HeLa细胞的作用及其机制。方法以HeLa细胞为试验材料,采用MTT法、比色法和流式细胞术等技术,分析葛根素对HeLa细胞的抑制作用。结果葛根素高、低剂量对HeLa细胞的半数抑制浓度(IC50)分别是48.31μg/ml和37.08μg/ml,提示葛根素不仅可明显抑制细胞生长,而且能显著上调HeLa细胞Caspase-3活性,并存在剂量和时间依赖性;通过对HeLa细胞周期测定,葛根素可影响肿瘤细胞内DNA复制和合成,抑制细胞正常分裂,阻滞细胞进入S期,从而使细胞在G1期堆积,出现G2/M阻滞,有丝分裂终止,从而抑制细胞增殖,导致肿瘤细胞凋亡。结论葛根素在体外能够抑制HeLa细胞生长,其机制可能与抑制细胞有丝分裂从而抑制增殖及上调Caspase-3活性有关。     

四株弓形虫在HeLa细胞内生长动态的观察

用HeLa细胞系研究了自国内分离的3株弓形虫的生长动态,并与RH株进行了比较。RH株弓形虫速殖子与HeLa细胞单层接触,只需2min,虫体便可侵入;而CN株需5min,ZS_2和PP株需10min。虫体侵入HeLa细胞至开始增殖,约经6h的迟滞期。通过计算各株不同孵育期纳虫泡内虫体数以及直线回归方程处理,发现RH株增殖一代的时间是5.2h,CN株是5.98h,ZS_2株是6.78h,PP株是7.69h。3株弓形虫中,以CN株对HeLa细胞的侵入力和增殖力与RH株最接近。     

齐墩果酸对宫颈癌细胞HeLa侵袭及凋亡的影响

目的探讨齐墩果酸对宫颈癌HeLa细胞侵袭以及细胞凋亡的影响。方法以HeLa细胞为研究对象,不同浓度的齐墩果酸处理细胞,CCK-8法观察其对HeLa细胞生长的抑制率;Transwell体外侵袭模型检测其对HeLa细胞侵袭能力的影响;Western blot检测不同浓度作用下HeLa细胞caspase-3、bcl-2蛋白表达的变化;ELISA检测各组细胞MMP-2、MMP-9的表达。结果齐墩果酸对对HeLa细胞的增殖及侵袭具有明显的抑制作用。0.2、0.4、0.8μmol/L的齐墩果酸作用下,HeLa细胞caspase-3的表达量分别比未处理组提高了0.31、0.80、0.98倍,而bcl-2的表达量分别降低了26.49%、49.72%和59.46%。不同浓度齐墩果酸作用下,HeLa细胞MMP-2和MMP-9的表达均有所下降,且呈一定的剂量依赖性。结论齐墩果酸可以抑制HeLa细胞的侵袭,并且诱导细胞的凋亡。     

白芷生物碱对HeLa细胞的抑制作用

目的探讨白芷生物碱(AAD)抑制HeLa细胞生长作用及其机制。方法采用MTT法、荧光染色法和流式细胞术,分析AAD对HeLa细胞的抑制和诱导凋亡作用。结果 AAD对Hela细胞生长具有明显抑制作用,且随着剂量增高而增高;其诱导HeLa细胞凋亡具有时间和剂量依赖性;AAD通过抑制Hela细胞分裂而降低其增殖能力。结论 AAD对HeLa细胞生长具有一定抑制作用,其作用机制可能与诱导HeLa细胞凋亡有关。     

玉米赤霉烯酮对HeLa细胞生长抑制作用和细胞超微结构损伤观察

目的观察ZEA对离体培养HeLa细胞的生长抑制作用和对超微结构影响,探讨其毒性作用机制。方法用四甲基偶氮唑蓝（MTT）检测不同剂量ZEA暴露24 h后,对HeLa细胞生长抑制作用。在透射电镜下观察ZEA所致细胞超微变化情况。结果 Hela细胞生长抑制率组间比较,差异有统计学意义（F=1 099.093,P〈0.05）;任何两组间细胞生长抑制率比较,差异有统计学意义（P〈0.05）;细胞生长抑制率随着染毒剂量的增加而增加。电镜下可见低剂量组细胞胞质内线粒体空泡变性和髓样变;高剂量组坏死细胞数量明显增多,细胞核固缩、畸变、崩解,线粒体嵴絮状变。结论 ZEA对Hela细胞有明显的细胞毒性作用并可导致细胞超微结构损伤。     

Telomerase activity in HeLa cervical carcinoma cell line proliferation

Normal human somatic cells in culture have a limited dividing potential. This is due to DNA end replication problem, whereby telomeres shorten with each subsequent cell division. When a critical telomere length is reached cells enter senescence. To overcome this problem, immortal HeLa cell line express telomerase, an enzyme that prevents telomere shortening. Although immortal, the existence of non-dividing cells that do not incorporate ³H-thymidine over 24 h of growth has been well documented in this cell line. Using DiI labeling and high-speed cell sorting, we have separated and analyzed fractions of HeLa cells that divided vigorously as well as those that cease divisions over several days in culture. We also analyzed telomerase activity in separated fractions and surprisingly, found that the fraction of cells that divided 0–1 time over 6 days in culture have several times higher endogenous telomerase activity than the fastest dividing fraction. Additionally, the non-growing fraction regains an overall high labeling index and low SA-β-Gal activity when subcultured again. This phenomenon should be considered if telomerase inhibition is to be used as an approach to cancer therapy. In this paper we also discuss possible molecular mechanisms that underlie the observed results.     

弯齿琵甲含药血清对宫颈癌HeLa细胞增殖的影响

目的探讨弯齿琵甲含药血清对宫颈癌HeLa细胞增殖的影响及其抗肿瘤的作用机制。方法采用血清药理学方法制备不同浓度的弯齿琵甲含药血清,MTT法检测不同浓度含药血清对宫颈癌HeLa细胞增殖的影响;显微镜下观察W right＇s-G iem sa染色和吖啶橙-EB染色后细胞的形态学变化;DNA琼脂糖凝胶电泳检测凋亡细胞DNA断裂情况。结果宫颈癌HeLa细胞经不同剂量的弯齿琵甲含药血清分别作用24、48 h后,细胞增殖明显受到抑制,且呈时效、量效关系;倒置显微镜下观察可见细胞膜皱缩,细胞核固缩,核染色质边缘化,并出现凋亡小体;荧光显微镜下可见早期凋亡细胞呈黄绿色球状,晚期凋亡细胞呈红色球状;凋亡细胞经琼脂糖凝胶电泳可观察到DNA梯形条带。结论弯齿琵甲含药血清对宫颈癌HeLa细胞增殖具有明显的抑制作用,其作用机制与诱导细胞凋亡相关。     

The effects of 1-methyl-1-nitrosourea on the survival pattern of cycling and noncycling HeLa cells

Summary The biological behavior of HeLa cells exposed to 1-methyl-1-nitrosourea was examined by determining the survival fraction in asynchronous and synchronous cultures. Asynchronous cell population exposed to 1-methyl-1-nitrosourea for 1 h exhibited a shoulder type survival curve, indicating that damage must be accumulated before the lethal effect occurs. A fraction of 25% of cells survives the concentration of 100 g/ml. The duration of treatment with the drug did not have a significant effect on the cell survival. The experiments with synchronized cells showed that MNU exhibits the killing in all phases of the cell age, but the most sensitive are these in S phase. However, they are still six times more resistant at the same concentration than the culture in plateau phase. At the concentration of 100 g/ml nondividing plateau cells are about 35 times more sensitive than exponentially growing cells. We can conclude that MNU acts as the most active killing agents on the cells which are in nondividing plateau phase.     

同型半胱氨酸促进血管平滑肌细胞增殖的机制及辛伐他汀的干预作用

目的:探讨同型半胱氨酸促进大鼠血管平滑肌细胞(VSMC)增殖的机制及辛伐他汀的干预作用。方法:贴壁培养的大鼠原代VSMC随机分为3组。(1)对照组:用含10%胎牛血清的DMEM培养基(完全培养基);(2)同型半胱氨酸组:在完全培养基中加入同型半胱氨酸(0.05 mmol/L);(3)辛伐他汀组:在完全培养基中加入同型半胱氨酸(0.05 mmol/L)和辛伐他汀(10μmol/L)。培养24 h后,光学显微镜下观察各组细胞的形态;采用半定量PCR法检测c-myc、P27kip1的mRNA水平;用Western blot检测细胞周期蛋白(cyclin)D1、cyclin E、cyclin A和核增殖抗原(PCNA)的蛋白表达水平。结果:与对照组相比,同型半胱氨酸组c-myc mRNA水平上调,P27kip1 mRNA水平下调,下游cyclin D1、cyclin E、cyclin A和PCNA蛋白表达增加。与同型半胱氨酸组相比,辛伐他汀组上述检测指标均得到逆转。结论:同型半胱氨酸可促进大鼠VSMC c-myc、cyclin D1、cyclin E、cyclin A等增殖相关基因的表达,抑制P27kip1表达。辛伐他汀可逆转上述效应。     

澳洲茄胺盐酸盐在三氧化二砷诱导的HeLa细胞凋亡中的作用及对细胞端粒酶活性的影响

目的 探讨澳洲茄胺盐酸盐(SBHL)在三氧化二砷(As2O3)诱导的HeLa细胞凋亡中的作用及对细胞端粒酶活性的影响.方法 采用细胞培养的方法体外培养宫颈癌HeLa细胞.用四甲基偶氮唑盐(MTT)法在SBHL(0,10,20,40,80,460,320 μmol/L)中筛选出最佳浓度.将HeLa细胞按1640培养液含As2O3和最佳SBHL浓度分为3组:对照组(0 μmol/L As2O3)、As2O3组(5 μmol/L As2O3)、As2O3+SBHL组(5μmoL/L As2O3+40μmol/L SBHL),培养时间分别为24、48、72 h.倒置显微镜下观察的HeLa细胞生长状况;透射电镜下观察HeLa细胞凋亡状况;MTT法检测HeLa细胞存活率;流式细胞术检测HeLa细胞周期和凋亡率;抗酒石酸酸性磷酸酶-酶联免疫(TRAP-ELISA)法检测HeLa细胞端粒酶活性的变化.结果 倒置相差显微镜下,对照组HeLa细胞排列密集,细胞呈圆形;As2O3组细胞数量减少,细胞间距逐渐增大;As2O3+SBHL组细胞收缩明显,细胞核碎裂为花瓣状,细胞间隙变得更大.电镜下,对照组Hela细胞表面有丰富的微绒毛,细胞间隔清晰,可见幼稚连接,连接不紧密,细胞核内多为常染色体,核仁清晰,核浆比约1∶1;As2O3组细胞超微结构呈现典型的凋亡特征,核内异染色质增多,染色质浓缩成块状,边集于核膜;As2O3+SBHL组细胞表面的微绒毛断裂、减少,核致密,呈块状分布,可见到凋亡小体.细胞存活率在24、48、72 h,组间比较差异均有统计学意义(X2分别为10.39、13.88、17.21,P均<0.05);在72 h,As2O3+SBHL组细胞存活率(52.80%)明显低于As2O3组(77.51%,X2=9.29,P<0.05).细胞周期G1期、S期组间比较差异有统计学意义(F值分别为7.46、22.14,P均<0.05);与对照组[(41.57±1.56)%、(50.45±2.37)%]比较,As2O3组[(27.10±5.32)%]和As2O3+SBHL组[(20.06±4.98)%]S期细胞减少(P<0.05或<0.01),G1期细胞增加[(58.70±5.18)%、(69.67±4.17)%,P<0.05或<0.01].细胞凋亡率组间比较差异有统计学意义(F=4.01,P<0.05);与对照组[(1.18±1.40)%]比较,As2O3组[(6.04±2.53)%]和As2O3+SBHL组[(21.08±1.22)%]细胞凋亡率明显升高(P<0.05或<0.01),其中As2O3+SBHL组高于As2O3组(P<0.01).端粒酶活性组间比较差异有统计学意义(F=21.28,P<0.05);与对照组(2.107±0.057)比较,As2O3组(1.214±0.621)和As2O3+SBHL组(0.865±0.284)细胞端粒酶活性降低(P均<0.05),其中As2O3+SBHL组低于As2O3组(P<0.05).结论 SBHL能促进As2O3诱导HeLa细胞凋亡,并能通过抑制端粒酶活性促进As2O3诱导HeLa细胞凋亡.

Abstract：

Objective To study whether solasodine hydrochloride (SBHL) could enhance the effect of arsenic trioxide in inducing apoptosis and affecting telomerase activity in cervical cancer HeLa cells. Methods Using cell culture methods, cervical cancer HeLa cells were cultured in vitro. The optimal concentration of SBHL was determined by MTT method from 0, 10, 20, 40, 80, 160, to 320 μmol/L. HeLa cells were grown in improved RPMI1640 supplemented respectively with arsenic trioxide(5 μmol/L As2O3), As2O3(5 μmol/L)+ SBHL( 40 μmol/L) and none (control group). The growth morphology of HeLa cells was observed under phase contrast microscopy after culture for 24, 48, and 72 h. Apoptosis of HeLa cells was determined under transmission electronic microscopy. The method of MTT was used to study the cell survival percentage. The technique of flow cytometry was used to measure cell cycle and cell apoptosis percentage. The method of tartrate-resistant acid phosphatase-enzyme linked immunosorbent assay (TRAP-ELISA) was used to determine telomerase activity of HeLa cells. Results Under phase contrast microscopy, in control group HeLa cells were round, densely packed; in As2O3 group the numbers of the cells were less, cell spacing increased; in As2O3 + SBHL group the cells shrinked significantly, nuclear fragmented as a petal-like, gap became larger. Under transmission electronic microscopy, there were rich microvillus on the cell surface in control group, cell intervals clear, immature connections, and the intervals did not close. The structure of the mitochondria in the cytoplasm was integrated. Most of the chromatin in the nucleus were, euchromatin and characteristics of apoptosis with heterochromatin increased and the chromatin condensed into masses, on the boundary of nuclear membrane. The microvillud on the cell surface were ruptured and decreased in As2O3 + SBHL group. The chromatin condensed into masses. The formation of apoptotic bodies was observed. The difference was statistically significant between groups in cell survival percentage at 24, 48, 72h(x2 = 10.39 , 13.88 , 17.21,respectively, all P < 0.05). Cell survival percentage in SBHL + As2O3 group (52.80%) was significantly less than that of As2O3 group(77.51%, x2 = 9.29, P < 0.05) at 72 h. In cell cycles, the difference was statistically significant between groups in C1 phase and S phase(F = 7.46,22.14, all P < 0.05), respectively. Compared with , control group[ (41.57 ± 1.56)%, (50.45 ± 2.37)%], cell percentages in S phase in As2O3 + SBHL group[(20.06 ± 4.98)%] and As2O3 group[(27.10 ± 5.32)%] were decreased(P< 0.05 or < 0.01), while cell percentage in C1 phase was increased[(58.70 ± 5.18)%, (69.67 ± 4.17)%, P< 0.05 or < 0.01]. The difference was statistically significant between groups in apoptotic percentage of HeLa cells (F = 4.01, P < 0.05). Compared with control group[ (1.18 ± 1.40)%], apoptosis percentage was significantly increased in As2O3 + SBHL group and As2O3 group [(21.08± 1.22)%, (6.04±2.53)%, P< 0.05 or < 0.01], respectively, and As2O3 + SBHL group was higher than As2O3 group(P < 0.01). The difference was statistically significant between groups in telomerase activity (F = 21.28, P< 0.05). Telomerase activity was inhibited in As2O3 group(1.214 ± 0.621) and As2O3A + SBHL group(0.865 ± 0.284) compared to control group (2.107 ± 0.057, all P < 0.05), and telomerase activity in As2O3 + SBHL group was lower than that of As2O3 group (P < 0.05). Conclusions SBHL enhances the effect of As2O3 in inducing apoptosis in HeLa cells, which is related to its inhibiting telomerase activity in HeLa cells.     

砷暴露对女性月经的影响

目的 探讨砷暴露对女性月经情况的影响.方法 2004年,采用整群抽样方法,对内蒙古巴彦淖尔市临河区、杭锦后旗和五原县5个乡10个社的所有10 ～ 65岁的女性,采集家中饮用水水样检测水砷,并按照水砷不同,调查对象分为对照组(≤0.01 mg/L)、低砷组(＞0.01～0.10 mg/L)、中砷组(＞0.10～0.20 mg/L)和高砷组(＞ 0.20 mg/L)进行月经相关情况调查.结果 共计调查602名女性,其中月经初潮前有砷暴露者83人,其月经初潮年龄为(14.37±1.54)岁;停经前有砷暴露者90人,停经年龄为(48.13±0.41)岁.经过相关性分析,月经初潮年龄和停经年龄与砷暴露年限均呈正相关,相关系数分别为0.268、0.278(P均＜0.05).与对照组[14.0％(16/112)]比较,中砷组月经异常率[18.2％(16/88)]有所增加,低砷组[12.1％(21/173)]、高砷组[10.2％(19/186)]有所降低,但4组比较差异无统计学意义(x2=3.664,P＞ 0.05).结论 长期砷暴露可以使女性月经的初潮年龄和停经年龄有所推迟,提示砷具有一定的内分泌干扰作用或雌激素样效应.     

雌激素对去卵巢大鼠胰岛β细胞数量和功能的影响

目的 观察大鼠在去卵巢和雌激素替代治疗状态下,经小剂量链脲佐菌素(STZ)干预后胰岛β细胞数量和功能的变化. 方法 30只雌性SD大鼠随机分为5组,正常对照组、STZ组、去卵巢组、去卵巢+STZ组和雌激素组.正常对照组和STZ组行假手术,其余均行去卵巢手术.术后雌激素组给予雌激素治疗,3周后STZ组、去卵巢+STZ组、雌激素组给予STZ(40 mg/kg)干预,检测各组大鼠血糖、血胰岛素水平,平均β细胞面积和相对β细胞数量,β细胞凋亡数量,β细胞内的促凋亡基因Bax、抗凋亡基因Bcl-2及增殖细胞核抗原(PCNA)蛋白表达水平. 结果 在STZ作用下,去卵巢大鼠口服葡萄糖耐量(OGTT)各时点血糖均较未去卵巢大鼠明显升高(P<0.05),且各时点胰岛素分泌水平均减少(P<0.05);胰岛素生成指数(△I30/△G30)及修正的β细胞胰岛素分泌指数MBCI下降,β细胞内胰岛素蛋白表达水平、相对β细胞数量和平均β细胞面积均明显下降(P<0.05),Bcl-2/Bax比值下降(0.41±0.03对0.76±0.05,P<0.05),β细胞的凋亡指数升高(t=2.957,P<0.05).去卵巢后给予雌激素替代治疗则对上述变化有明显的改善作用,OGTT各时点血糖水平显著下降(P<0.05),β细胞内胰岛素蛋白表达水平及血胰岛素水平的升高,Bcl-2/Bax比值上升(0.71±0.05对0.41±0.03),β细胞的凋亡指数下降(t=2.782,P<0.05). 结论 去卵巢大鼠对外来刺激明显易感,小剂量STZ即导致胰岛β细胞的凋亡增加,数量减少,胰岛素分泌水平的下降,血糖明显升高.补充雌激素能够对抗去卵巢带来的对胰岛β细胞的不利影响,改善β细胞的凋亡,具有保护作用.     

Assessment of multidrug resistance on cell coculture patterns using scanning electrochemical microscopy

The emergence of resistance to multiple unrelated chemotherapeutic drugs impedes the treatment of several cancers. Although the involvement of ATP-binding cassette transporters has long been known, there is no in situ method capable of tracking this transporter-related resistance at the single-cell level without interfering with the cell’s environment or metabolism. Here, we demonstrate that scanning electrochemical microscopy (SECM) can quantitatively and noninvasively track multidrug resistance-related protein 1–dependent multidrug resistance in patterned adenocarcinoma cervical cancer cells. Nonresistant human cancer cells and their multidrug resistant variants are arranged in a side-by-side format using a stencil-based patterning scheme, allowing for precise positioning of target cells underneath the SECM sensor. SECM measurements of the patterned cells, performed with ferrocenemethanol and [Ru(NH₃)₆]³⁺ serving as electrochemical indicators, are used to establish a kinetic “map” of constant-height SECM scans, free of topography contributions. The concept underlying the work described herein may help evaluate the effectiveness of treatment administration strategies targeting reduced drug efflux.     

Urocortin2 inhibits tumor growth via effects on vascularization and cell proliferation

The corticotropin-releasing factor (CRF) receptor CRFR2 is expressed widely in peripheral tissues and in the vasculature, although its functional roles in those tissues have only recently begun to be elucidated. Previously we found that genetic deletion of CRFR2 resulted in profound postnatal hypervascularization in mice, characterized by both an increase in total vessel number and a dramatic increase in vessel diameter. These data strongly suggested that ligands for CRFR2 act to limit tissue vascularity, perhaps as a counterbalance to factors that promote neovascularization. Urocortin 2 (Ucn2) is a specific ligand for the CRFR2. We hypothesized that activation of CRFR2 by Ucn2 might thus suppress tumor vascularization and consequently limit tumor growth. Here, we show that viral-mediated expression of Ucn2 strikingly inhibits the growth and vascularization of Lewis Lung Carcinoma Cell (LLCC) tumors in vivo. Further, we found that this effect on tumor growth inhibition was independent of whether exposure to Ucn2 occurred before or after establishment of measurable tumors. In vitro, Ucn2 directly inhibited the proliferation of LLCC, suggesting that the tumor-suppressing effects of CRFR2 activation involve a dual mechanism of both a direct inhibition of tumor cell cycling and the suppression of tumor vascularization. These results establish that Ucn2 inhibits tumor growth, suggesting a potential therapeutic role for CRFR2 ligands in clinical malignancies.