去泛素化酶USP9X在宫颈鳞癌中的表达及临床意义

目的:探讨X染色体连锁的泛素特定蛋白水解酶9（ubiquitin-specific peptidase 9 X-linked,USP9X）在宫颈鳞癌中的表达及临床意义。方法:应用EnVision法免疫组织化学技术对宫颈无上皮内瘤变或其他恶性病变组织（negative for intraepithelial lesion or malignancy,NILM）、低级别上皮内瘤变（lower grade squamous intraepithelial lesion,LSIL）、高级别上皮内瘤变（high grde squmous intrepithelil lesion,HSIL）各40例及宫颈鳞癌（cervical squamous-cell carcinoma,CSCC）标本85例中的USP9X蛋白水平进行检测;蛋白印迹法（Western-Blot）检测宫颈癌细胞SiHa中USP9X蛋白的水平。结果:USP9X从宫颈正常上皮到宫颈鳞癌的逐级病变中其表达水平逐步升高: NILM（5.0%）、LSIL（12.5%）、HSIL（40.0%）、CSCC（60.0%）;SiHa细胞培养中,顺铂(C-DDP)处理组USP9X蛋白表达水平较对照组明显降低。结论:USP9X表达的上调可能参与了宫颈癌的发生与发展,可作为宫颈癌治疗时重要参考及预后指标,有望成为宫颈癌的一个潜在治疗靶点。     

Analysis of chromosomes 3, 7, X and the EGFR gene in uterine cervical cancer progression

The aim of this study was to investigate the possible role of genetic alterations in the genesis and progression of cervical carcinomas. We analysed the 3, 7, X aneusomy of chromosomes and the status of the epidermal growth factor receptor (EGFR) gene by fluorescence in situ hybridisation (FISH) analysis. Polysomy of chromosomes 3 and X defined the transition from high-grade squamous intraepithelium lesions (HSIL) to cervical carcinoma. Chromosome 7 monosomy and polysomy did not show any statistical significant differences between the groups examined. When we compared the chromosomal aneusomies in all of the specimens using the Kruskal-Wallis test, significant differences (P = 0.0001, P = 0.0001 for chromosomes 3 and X, respectively) were observed. Using a ratio of the EGFR gene signals and chromosome 7 centromeric signals, no samples showed gene amplification. Our results demonstrate the importance of chromosomal 3 and X aneusomies in the development and progression from HSIL to cervical carcinoma, highlighting their usefulness as genetic markers for identifying SILs at high-risk of progression.     

Clonal Identification of Trisomies 3, 5 and X in Angioimmunoblastic Lymphadenopathy with Dysproteinemia by Fluorescence in situ Hybridization

Trisomies 3, 5 and X in six Japanese patients with AILD were detected by fluorescence in situ hybridization (FISH). Trisomies 3 and X were detected using centromeric probes. Cosmid probes locating on 5q31.1, the commonly deleted region, was used to detect trisomy 5. FISH detected three patients with trisomy 3 alone, one with trisomy 5 alone and one with all the three trisomies analysed. The sample that showed all three aberrations was further analysed by dual color FISH. The three trisomies were present on different cells. The AILD cells with trisomy 5 tended to replicate slowly, whereas those with trisomy 3 seem to have a proliferative advantage. An increase in the histopathological stage was reflected in the increase in the percentage of trisomy 3 cells in one patient.     

乙型肝炎病毒X蛋白对肝癌细胞MKK3,p38MAPK表达的影响

目的：观察乙型肝炎病毒X蛋白对肝癌细胞中丝裂原活化蛋白激酶（MKK3）及其下游分子p38丝裂酶原活化的蛋白激酶（p38MAPK）的表达的影响,探讨相关的信号转导机制,及其对肝癌细胞生物学行为的影响。方法：分别将质粒pCDNA3.1及pCDNA3.1-HBx重组质粒经脂质体介导转染人肝癌细胞株HepG2,G418筛选培养,并用反转录PCR和Western blot鉴定,获得表达X蛋白的稳定细胞株HepG2-HBx和阴性对照细胞株HepG2-pCDNA3.1,以HepG2细胞株作空白对照。通过RT-PCR和Western blot检测上述三种细胞株中MKK3,p38MAPK在mRNA水平和蛋白水平的表达变化,并用细胞免疫荧光法检查磷酸化p38MAPK蛋白在细胞浆及细胞核中的变化;通过MTT实验检测三种细胞株的增殖情况。采用SPSS 12软件进行统计学分析。结果：MKK3在mRNA和总蛋白水平的表达在HepG2-HBx中均高于其他两组,其他两组无明显差异;p38MAPK在mRNA和总蛋白水平三组无明显差异,而其蛋白磷酸化水平和在核蛋白中的表达在HepG2-HBx中较其他两组升高;HepG2-HBx较其他两组细胞有更强的增殖能力。结论：HBx可以通过上调肝癌细胞中MKK3的表达,促进p38MAPK磷酸化和入核,从而进一步激活下游分子发挥生物活性。p38MAPK通路在HBx促进肝癌细胞的增殖中发挥重要作用。可能是导致HBV相关性肝癌与非HBV相关性肝癌临床特点及肿瘤生物学差异的机制之一。     

乙型肝炎病毒X蛋白对肝癌细胞MKK3,p38MAPK表达的影响

目的:观察乙型肝炎病毒X蛋白对肝癌细胞中丝裂原活化蛋白激酶(MKK3)及其下游分子p38丝裂酶原活化的蛋白激酶(p38MAPK)的表达的影响,探讨相关的信号转导机制,及其对肝癌细胞生物学行为的影响。方法:分别将质粒pCDNA3.1及pCDNA3.1-HBx重组质粒经脂质体介导转染人肝癌细胞株HepG2,G418筛选培养,并用反转录PCR和Western blot鉴定,获得表达X蛋白的稳定细胞株HepG2-HBx和阴性对照细胞株HepG2-pCDNA3.1,以HepG2细胞株作空白对照。通过RT-PCR和Western blot检测上述三种细胞株中MKK3,p38MAPK在mRNA水平和蛋白水平的表达变化,并用细胞免疫荧光法检查磷酸化p38MAPK蛋白在细胞浆及细胞核中的变化;通过MTT实验检测三种细胞株的增殖情况。采用SPSS 12软件进行统计学分析。结果:MKK3在mRNA和总蛋白水平的表达在HepG2-HBx中均高于其他两组,其他两组无明显差异;p38MAPK在mRNA和总蛋白水平三组无明显差异,而其蛋白磷酸化水平和在核蛋白中的表达在HepG2-HBx中较其他两组升高;HepG2-HBx较其他两组细胞有更强的增殖能力。结论:HBx可以通过上调肝癌细胞中MKK3的表达,促进p38MAPK磷酸化和入核,从而进一步激活下游分子发挥生物活性。p38MAPK通路在HBx促进肝癌细胞的增殖中发挥重要作用。可能是导致HBV相关性肝癌与非HBV相关性肝癌临床特点及肿瘤生物学差异的机制之一。     

Deubiquitinase ubiquitin‐specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells

The E3 ubiquitin ligase ring finger protein 115 (RNF115) is overexpressed in more than half of human breast tumors and is implicated in the pathogenesis and progression of breast cancer. However, the mechanism behind RNF115 overexpression in breast tumors remains largely unknown. Here we report that ubiquitin‐specific protease 9X (USP9X), a substrate‐specific deubiquitinating enzyme, stabilizes RNF115 and thereby regulates its biological functions in breast cancer cells. Immunoprecipitation and GST pull‐down assays showed that USP9X interacted with RNF115. Depletion of RNF115 by siRNAs or overexpression of RNF115 did not significantly affect USP9X expression. In contrast, knockdown of USP9X in breast cancer cells by siRNAs reduced RNF115 protein abundance, which was partially restored following treatment with proteasome inhibitor MG‐132. Moreover, depletion of USP9X reduced the half‐life of RNF115 and increased its ubiquitination. Conversely, overexpression of USP9X resulted in an accumulation of RNF115 protein, accompanied by a decrease in its ubiquitination. RNF115 mRNA levels were unaffected by overexpression or knockdown of USP9X. Furthermore, USP9X protein expression levels correlated positively with RNF115 in breast cancer cell lines and breast tumor samples. Importantly, reintroduction of RNF115 in USP9X‐depleted cells partially rescued the reduced proliferation, migration, and invasion of breast cancer cells by USP9X knockdown. Collectively, these findings indicate that USP9X is a stabilizer of RNF115 protein and that the USP9X‐RNF115 signaling axis is implicated in the breast cancer malignant phenotype.     

结直肠癌组织STAT3和MMP-9表达及其与血管生成相关性的研究

目的:探讨结直肠癌组织中信号转导与转录激活因子3(STAT3)和基质金属蛋白酶-9(MMP-9)的表达及其与血管生成的相关性。方法:应用免疫组化SP法检测60例结直肠癌组织和20例癌旁正常组织中STAT3和MMP-9的表达,以及CD-105标记的微血管密度(MVD)情况。结果:STAT3和MMP-9在结直肠癌组织中阳性表达率分别为61.7%和73.3%,明显高于癌旁正常组织的30.0%和35.0%,P值均<0.05。癌组织中MVD值为36.02±9.74,明显高于癌旁正常组织11.25±7.35,t=11.97,P<0.01。癌组织中STAT3和MMP-9均阳性表达时MVD值明显高于均阴性组或单一阳性组,P值均<0.01。STAT3、MMP-9和MVD三者均与肿瘤分化程度、Duke分期、淋巴结转移及肝转移相关,P值均<0.05;而与年龄、性别及肿瘤大小无关,P值均>0.05。结论:STAT3、MMP-9及MVD的高表达与结直肠癌的浸润及转移有关,联合检测3项指标对判断结直肠癌的侵袭转移及预后有重要意义。     

卵巢浆液性肿瘤中凋亡调控因子Smac Caspase-9和Caspase-3的表达及意义

目的:探讨凋亡调控因子Smac、Caspase-9和Caspase-3在卵巢浆液性肿瘤中的表达。方法:采用免疫组织化学技术(SP法)和图像分析技术检测25例卵巢浆液性囊腺癌、10例卵巢交界性浆液性囊腺瘤、30例卵巢浆液性囊腺瘤和24例正常卵巢组织中凋亡调控因子Smac、Caspase-9和Caspase-3表达水平。结果:Caspase-3、Caspase-9和Smac在30例浆液性囊腺瘤中的表达率分别为93%、93%和73.3%;在10例交界性浆液性囊腺瘤中的表达率分别为70%、80%和80%;在25例浆液性囊腺癌中的表达率分别为96%、96%和84%。阳性信号主要定位于细胞质,呈弥漫分布。而在正常卵巢24例中的表达率分别为83.3%、80.9%和58.3%。凋亡调控因子Caspase-3、Caspase-9和Smac在浆液性卵巢肿瘤中的表达增加(P<0.05)。结论:凋亡调控因子Caspase-3、Caspase-9和Smac在卵巢浆液性肿瘤中的表达增加。这提示Caspase-3、Caspase-9和Smac可能会成为卵巢浆液性肿瘤治疗的新靶点。     

胃癌组织中CD44V9和nm23蛋白的表达及其相关性研究

目的　探讨胃癌组织中 CD44 V9和 nm2 3的表达、相关性及其临床意义。方法　采用免疫组化 SABC法对 60例胃癌中 CD44 V9和 nm2 3表达进行检测。结果　胃癌组织中 CD44 V9和 nm2 3的阳性表达率分别为75 .0 %和 5 5 .0 % ;CD44 V9阳性胃癌中 nm2 3阳性表达率 (42 .2 % )明显低于 CD44 V9阴性胃癌 (93 .3 % ) (P<0 .0 0 1)。 CD44 V9阳性表达与胃癌 L auren分型、浸润深度 ,淋巴结转移及 TNM分期有关 (P<0 .0 1) ;nm2 3表达与胃癌淋巴结转移有关 (P<0 .0 5 )。结论　 CD44 V9和 nm2 3在胃癌中表达呈明显负相关 ,两者均有可能作为临床上预测胃癌侵袭转移潜能的指标     

Characterization of a novel epigenetically-silenced, growth-suppressive gene, ADAMTS9, and its association with lymph node metastases in nasopharyngeal carcinoma

By using a functional complementation approach, suppression of tumorigenicity was observed after transfer of intact or truncated copies of chromosome 3 into a nasopharyngeal carcinoma (NPC) HONE1 cell line. The extra exogenous chromosome 3 in the microcell hybrids (MCHs) significantly extended the lag period of tumor formation, which may be associated with loss or inactivation of wild type alleles from the normal donor chromosome 3. Representative tumors, which grew in nude mice were reconstituted into culture and expanded as tumor segregants (TSs). In our study, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9), a gene mapping to 3p14.2, was identified to be critically associated with tumor suppression in NPC. Gene expression analysis showed that ADAMTS9 was either not expressed or was downregulated in HONE1 cells, TSs and NPC cell lines. The mechanism of ADAMTS9 gene inactivation in the NPC cell lines and tissues was attributed to promoter hypermethylation. Using a tissue microarray and immunohistochemical staining, 31 of 66 (47%) of the NPC cases showed downregulated or absence of ADAMTS9 expression. ADAMTS9 expression was downregulated or lost in 17 of 23 (73.9%) lymph node metastatic NPC specimens, which was significantly higher than in 14 of 43 (32.6%) primary tumors. After transfection of the ADAMTS9 gene into 7 NPC cell lines, a dramatic reduction of colony forming ability was observed. These findings support ADAMTS9 as a putative tumor suppressor gene in vivo in NPC that is significantly associated with lymph node metastases.     

PCNA、P16、MMP9在人参皂甙Rg3抗肝癌淋巴道转移中的表达及意义

目的 :通过检测PCNA、P16及MMP 9在人参皂甙Rg3抗荷瘤小鼠淋巴道转移中的表达 ,探讨人参皂甙Rg3抗肿瘤作用的机制。方法 :建立小鼠肝癌淋巴道转移模型 ,应用免疫组织化学方法检测PCNA、P16及MMP 9在各实验组 (Rg3预防组、Rg3治疗组、Rg3+DDP合用组、DDP阳性对照组和生理盐水阴性对照组 )的原发瘤及相应转移瘤 (淋巴结 )中的表达水平。结果 :应用人参皂甙Rg3组较未用药组 ,PCNA及MMP 9在原发瘤的表达减少 ,P16的表达增加 ,差异显著 (P <0 0 0 1) ;而在转移瘤中的变化不明显。结论 :人参皂甙Rg3抗淋巴道转移作用的机制与上调P16表达及下调PCNA和MMP9表达有关。     

青蒿琥酯对人肺腺癌A549细胞中caspase-9及caspase-3活性的影响

 目的 研究青蒿琥酯（artesunate,Art）体外诱导人肺腺癌A549细胞凋亡及对半胱天冬氨酸蛋白酶9（cysteine containing aspartate9,caspase-9）和caspase-3活性的影响。方法 Art处理A549细胞,流式细胞计数（Flow Cytometry,FCM）检测细胞周期和细胞凋亡,比色法检测caspase-9活性,westernblot检测caspase-3变化。结果 FCM显示A549细胞经100mg/L Art作用24h,出现S期细胞减少（P〈0.01）,G2/M期细胞数目增多（P〈0.01）,细胞凋亡率增加（P〈0.0）。不同浓度（10mg/L、25mg/L、50mg/L、100mg/L）的Art作用A549细胞24h,caspase-9活性呈浓度依赖性增加,分别为对照组的9.87倍、23.33倍（P〈0.01）、38.47倍（P〈0.01）和60.47倍（P〈0.01）。Western blot显示A549细胞经100mg/L Art作用6、12、24h后,细胞浆中caspase-3活化,分别为对照组1.2倍、1.6倍（P〈0.01）、1.8倍（P〈0.01）。结论 青蒿琥酯可通过增加caspase-9和caspase-3的活性,诱导A549细胞凋亡,为阐明Art的抗癌机理,指导青蒿琥酯用于肿瘤治疗提供实验依据。     

血浆基质金属蛋白酶-9在胃癌中表达及与侵袭、转移关系探讨

目的检测胃癌患者血浆基质金属蛋白酶-9在胃癌中表达及其临床意义。方法采用抗MMP-9MOAb建立了MMP-9血浆酶免疫测定法。检测血浆基质金属蛋白酶-9在胃癌中的阳性表达率及其与胃癌的病理类型、淋巴结转移、侵袭程度的关系。结果胃癌组36例,阳性率50%(18/36),对照组20例,阳性率5%(1/20),两组差异有显著性(P<0.01)。血浆基质金属蛋白酶-9与胃癌的侵袭程度、淋巴结转移密切相关(P<0.01),与胃癌的病理类型无关(P>0.05)。结论胃癌患者血浆基质金属蛋白酶-9较对照组明显增高,且与胃癌侵袭程度,淋巴结转移密切相关。血浆基质金属蛋白酶-9的检测,是对胃癌前病变监测及判断胃癌的生物学特征重要指标,对胃癌的预后评估具有重要的临床意义。     

N2-3期鼻咽癌下颈锁骨上区照射中间设置不同宽度铅挡块的剂量学研究

背景与目的:N2-3期鼻咽癌常规照射时,需设置中间挡铅的前切线野照射下颈锁骨上淋巴引流区,目前对于中间铅挡块宽度仍有不同的做法,本研究通过应用三维治疗计划系统(three-dimensional treatment planning system,3D-TPS)对前切线野照射下颈锁骨上区的剂量分布进行分析.探讨合适宽度的铅挡块.方法:选取初治N2-3期鼻咽癌患者10例,采用3D-TPS设计照射方案.每例患者均采用逐步缩野照射技术.下颈锁骨上区均设置单前切线野,前40 Gy中间分别采用铅挡0 cm(A方案)、2.1 cm(B方案)、2.5 cm(C方案)、3.0 cm(D方案),之后中间均挡3.0 cm 4种方案.每例患者的4种方案照射剂量均相同.比较4种照射方案的靶区及主要危及器官的受照体积和剂量.结果:(1)4种方案下颈锁骨上亚临床病灶区(PTV50a)的高剂量区覆盖率(V95、V90)比较:A方案(82.44%、87.89%)优于B方案(78.21%、84.03%)、C方案(77.10%、82.68%)、D方案(73.80%、77.50%)(P＜0.05);B方案、C方案好于D方案(P＜0.05);B方案与C方案比较无统计学意义(P＞0.05).而对于原发灶大体肿瘤区(PTVnx)、颈部转移淋巴结(PTVnd)、原发灶周围高危区(PTVnx60)、转移淋巴结周围高危区(PTVnd60)及环状软骨以上的亚临床病灶区(PTV50b)的V95、V90,4种方案之间比较差异均无统计学意义(P＞0.05).(2)4种方案脊髓、喉的受照剂量无统计学意义;甲状腺、食管、气管的受照剂量(D50):A方案(49.47、44.52、44.18 Gy)高于B方案(41.95、8.41、10.16 Gy)、C方案(38.73、7.03、8.55 Gy)、D方案(26.82、5.63、7.60 Gy)(P＜0.05);B方案、C方案均高于D方案(P＜0.05);B方案、C方案比较无统计学意义(P＞0.05).(3)正常组织并发症发生率(NTCP)的比较:甲状腺的NTCP,A方案(7.9%)高于B方案(4.8%)、C方案(4.3%)、D方案(3.0%)(P＜0.05);B方案、C方案均高于D方案(P＜0.05);B方案、C方案之间比较无统计学意义(P＞0.05).其余主要危及器官的NTCP,4种方案比较差异无统计学意义(P＞0.05).结论:在不明显增加主要危及器官受照剂量的情况下,A方案有最优的下颈锁骨上区亚临床病灶高剂量区覆盖率,D方案最差;行下颈锁骨上区照射时,我们推荐前40 Gy中间不设铅挡块,之后选用个体化铅挡块.对于头颈部摆位误差小的单位,建议采用铅挡块宽度≥2.1 cm、≤2.5 cm.     

CA-9、CD1a、CD3和EGFR在Ⅰ期非小细胞肺癌中的表达及临床意义

目的：研究低氧标记物CA-9、肿瘤侵袭相关的EGFR表达、与肿瘤免疫功能有关的DC,T淋巴细胞浸润、以及肿瘤坏死程度在Ⅰ期非小细胞肺癌患者中的临床和预后意义.方法：应用免疫组化法检测59例Ⅰ期非小细胞肺癌患者的CA-9、CD1a、CD3和ECFR的表达.结果：CD1a、CD3和EGFR在腺癌中的表达明显高于鳞癌（P＜0.05）;CA-9高表达和肿瘤高坏死者,其肿瘤中的CD1a浸润低（火0.05）;肿瘤高坏死的患者,生存率明显低于低坏死者（P＜0.05）;术后化疗组与未化疗组在生存率上未发现有显著性差异,但进一步分层分析显示：在CA-9阳性表达和CD1a阴性的患者中,术后化疗组的生存率明显短于未行化疗组（P＜0.05）.结论：非小细胞肺癌早期即有免疫细胞的浸润,肿瘤低氧、不同病理学类型和肿瘤的坏死程度可能影响免疫细胞的浸润;肿瘤的坏死程度影响患者的生存率;检测CA-9和CD1a的表达可能对Ⅰ期非小细胞肺癌患者术后是否应该化疗有指导意义.     

结直肠癌组织MMP-7、MMP-9表达与腹腔微转移的相关性研究

目的:探讨MMP-7、MMP-9在结直肠癌腹腔微转移中的作用以及相关性。方法:收集98例结直肠癌患者手术中腹腔冲洗液,进行CEA、CK20免疫细胞化学染色确定腹腔微转移。使用组织阵列仪制作组织芯片,进行免疫组化染色(SP),检测MMP-7、MMP-9在结直肠癌组织中的表达情况,分析其与腹腔微转移的关系。结果:CEA、CK20联合检测腹腔微转移率为32.7%(32/98)。MMP-7、MMP-9在伴有腹腔微转移的结直肠癌中阳性表达率分别为93.75%和96.88%,明显高于无腹腔微转移结直肠癌表达率72.73%和68.18%(P<0.05,P<0.01)。结论:MMP-7、MMP-9可能在结直肠癌腹腔微转移的发生过程中起重要作用。     

Dietary intake of fish, ω‐3 and ω‐6 fatty acids and risk of colorectal cancer: A prospective study in U.S. men and women

The association between fish, ω‐3 and ω‐6 polyunsaturated fatty acid (PUFA) intake and risk of colorectal cancer (CRC) remains inconclusive. Recent prospective studies suggest that the relationship may vary by gender, subsite and duration of follow‐up. We followed 123,529 US adults (76,386 women and 47,143 men) without a history of cancer at baseline for 24 to 26 years. Fish and PUFA intake was assessed at baseline and updated every 4 years by using a validated food‐frequency questionnaire. We found no overall association between fish, ω‐3 and ω‐6 PUFA intake and CRC risk with hazard ratio (HR) of 1.03 [95% confidence interval (CI): 0.89–1.20] comparing marine ω‐3 intake of ≥0.30 g/d versus <0.15 g/d among women and 1.05 (95% CI: 0.85–1.30) comparing intake of ≥0.41 g/d versus <0.16 g/d among men. However, fish and marine ω‐3 PUFA intake appeared to be positively associated with risk of distal colon cancer in both men and women and inversely with risk of rectal cancer in men. In an analysis based on a limited number of cases, marine ω‐3 PUFA intake assessed 12–16 years before diagnosis tended to be inversely associated with CRC risk in men (HR: 0.76; 95% CI: 0.52–1.10). In conclusion, although no overall association between fish, ω‐3 or ω‐6 PUFA intake was observed with CRC risk, marine ω‐3 PUFA may be differentially associated with risk of distal colon and rectal cancers and a long latency may be needed for its protection against CRC in men.     

蛋白酶体抑制剂联合pshSTAT3对喉癌细胞增殖及凋亡的影响

背景与目的:蛋白酶体抑制剂是一种新型抗肿瘤靶向治疗药物,其作用机制复杂.本研究前期的工作已经证实,蛋白酶体抑制剂可以有效抑制人喉鳞癌Hep-2细胞的增殖并诱导其凋亡,但它同时也诱导了p-STAT3蛋白表达水平的升高.本研究旨在探讨pshSTAT3抑制p-STAT3蛋白表达能否增强蛋白酶体抑制剂MG-132对喉癌细胞的抗肿瘤作用.方法:以Hep-2细胞为实验对象,利用四甲基偶氮唑蓝(MTT)法、流式细胞术(flow cytometry,FCM)检测MG-132单独及联合pshSTAT3时,细胞增殖抑制率及凋亡率的变化;Western印迹法检测各组p-STAT3蛋白表达情况.结果:MTT榆测结果显示,联合组细胞的增殖抑制作用最强,与MG-132组及pshSTAT3组相比较差异均有统计学意义(P＜0.01).FCM检测结果显示,联合组细胞出现明显的凋亡峰,其凋亡率显著高于MG-132组和pshSTAT3组,差异极有统计学意义(P＜0.01).Western印迹法检测结果显示,经2.5μmol/L MG-132处理Hep-2细胞后P-STAT3蛋白表达显著增强;联合组及pshSTAT3组P-STAT3蛋白表达明显减弱.结论:pshSTAT3可以抑制MG-132诱导的p-STAT3蛋白表达,从而提高蛋白酶体抑制剂MG-132对喉癌细胞的抗肿瘤作用.