鼻咽癌组织与外周血CD4+CD25+调节性T细胞检测及临床意义

 目的 通过检测鼻咽癌患者肿瘤组织及外周血中CD4⁺T、CD8⁺T、CD4⁺CD25^-T、CD4⁺CD25⁺T细胞的频数,寻找客观、全面评价鼻咽癌患者免疫状态的临床指标。方法 采用流式细胞术检测40例初诊鼻咽癌患者及10例正常对照鼻咽部组织和外周血CD4⁺T、CD8⁺T、CD4⁺CD25^-T、CD4⁺CD25⁺T细胞比例。结果 鼻咽癌患者CD4⁺T细胞比例及CD4⁺/ CD8⁺T比值均低于对照组（P<0.05）,而CD8⁺T细胞两组间差异无统计学意义（P>0.05）,但是CD4⁺/ CD8⁺T比值在鼻咽癌组织与外周血间差异无统计学意义（P>0.05）。鼻咽癌组织及外周血中CD4⁺CD25⁺T细胞比例都高于对照组（P<0.05）,同时癌组织中该细胞比例远远高于外周血（P<0.05）。在鼻咽癌组织中CD4⁺CD25⁺T细胞与CD8+ T细胞、CD4⁺CD25^-T细胞呈负相关（r分别为-0.70、-0.675,P<0.05）,而在外周血中没有相关关系（P>0.05）。在不同T(原发肿瘤大小)组间,T4组的鼻咽癌组织中CD4⁺CD25⁺T细胞分别高于T1、T2、T3各组（P<0.05）,而在T1、T2、T3各组间差异无统计学意义（P>0.05）;鼻咽癌中CD4⁺CD25⁺T细胞比例与患者有无淋巴结转移并无关系（P>0.05）;鼻咽癌组织中Ⅲ+Ⅳ期组CD4⁺CD25⁺T细胞比例高于Ⅰ+Ⅱ期组（P<0.05）,而在外周血中两组间差异无统计学意义（P>0.05）。结论 CD4⁺CD25⁺T细胞与鼻咽癌病程进展无相关性,但是联合检测患者肿瘤组织及外周血中CD4⁺CD25⁺T细胞的频数并结合既往CD4⁺/ CD8⁺T比值会全面反应患者免疫状态,为临床治疗提供依据。     

CD44V 3 基因蛋白在胃癌中的表达及意义

 细胞粘附分子 CD44 是一种细胞表面跨膜糖蛋白 ,为了解 CD₄₄V ³ 表达与胃癌之间的关系 ,本文采用免疫组化 S- P染色方法 ,研究了 CD₄₄V ³ 在胃癌组织的表达情况 ,并探讨其临床病理意义。     

CD44V 3 基因蛋白在胃癌中的表达及意义

细胞粘附分子 CD44 是一种细胞表面跨膜糖蛋白 ,为了解 CD₄₄V ³ 表达与胃癌之间的关系 ,本文采用免疫组化 S- P染色方法 ,研究了 CD₄₄V ³ 在胃癌组织的表达情况 ,并探讨其临床病理意义。     

恶性肿瘤患者外周血CD146＋T淋巴细胞的检测及其临床意义

 目的 探讨CD146^＋T淋巴细胞在肿瘤患者外周血中的变化及其临床意义。 方法 用流式细胞术检测47例健康对照组和188例肿瘤患者外周血中CD3^＋CD146^＋T淋巴细胞的数量,并观察其在肿瘤疾病中的变化。 结果 （1）与健康对照组比较,总肿瘤组、肝癌、肺癌组、食管癌、乳腺癌、胃癌、胰腺癌组的CD146^＋T/T比例显著升高,差异有统计学意义（P<0.001）。（2）与健康对照组比较,肿瘤组的外周血T细胞绝对数是降低的（P<0.05）,而CD146^＋T绝对数却是与健康对照相似（P>0.05）;（3）恶性肿瘤患者外周血CD146⁺ T比例与T细胞绝对计数负相关（n=188,r=-0.297,P<0.001）。（4）肿瘤转移组与未转移组的CD146^＋T/T比例的比较未观察到差异有统计学意义（P>0.05）。 结论 肿瘤患者外周血CD146^＋T比例增高,可能是机体抗肿瘤免疫调节的一个重要方面。     

CD44+/CD24-表型与BRCA1及basal-like乳腺癌的相关性

 目的：探讨CD44⁺/CD24^-表型与BRCA1及basal-like乳腺癌的相关性。方法：收集经病理诊断为乳腺癌患者的手术切除石蜡标本共217例,根据免疫学标志物把217例乳腺癌划分为5类分子亚型：basal-like型、luminal A型、luminal B 型、Her2过表达型和normal breast-like型。应用免疫组织化学检测CK5/6、BRCA1和CD44/CD24双染的情况,分析CD44⁺/CD24^-表型与basal-like乳腺癌及BRCA1相关性乳腺癌的关系。结果：217例乳腺癌标本例中,luminal A型130例、luminal B型15例、HER2过表达型21例、basal-like型29例、Normal breast-like型22例。BRCA1相关性乳腺癌57例。basal-like乳腺癌组织中BRCA1缺失率86%（25/29）,明显高于乳腺癌其他分子亚型(P<0.001)。basal-like乳腺癌组织中含CD44⁺/CD24^-肿瘤细胞者20例 (20/29,69%),明显高于乳腺癌其他分子亚型(P=0.003);BRCA1相关性乳腺癌中含CD44⁺/CD24^- 肿瘤细胞者53例(53/57,93%)。结论：BRCA1基因突变与basal-like乳腺癌有关;CD44⁺/CD24^-干细胞表型主要存在于basal-like乳腺癌及BRCA1相关性乳腺癌中。     

香加皮杠柳苷对MCF-7细胞周期及p21WAF1/CIP1表达的影响

 目的：研究香加皮杠柳苷（CPP）对人乳腺癌MCF-7细胞周期及p21^WAF1/CIP1表达的影响 ,探讨其抗肿瘤作用及作用机制。方法：采用MTT法检测不同浓度CPP（1.25、2.50、5.00、 10.00、20.00 ng/ml）作用不同时间（24、48、72 h）对MCF-7细胞的增殖抑制作用;应用流 式细胞术分析不同浓度CPP （2.50、5.00、10.00 ng/ml）分别作用于MCF-7细胞6、12、24、 48、72 h对肿瘤细胞周期的影响;并采用RT-PCR和免疫细胞化学技术检测细胞周期相关因子 p21^WAF1/CIP1的表达。结果：CPP能明显抑制MCF-7细胞的增殖,并呈浓度及时间依赖性,作用 于MCF-7细胞48 h的IC₅₀为（4.88±0.16）ng/ml。流式细胞术结果显示,CPP作用MCF-7细胞24 h时,G₀/G₁期细胞明显增多,而S期和G₂/M期细胞显著减少,与对照组相比差异有统计学意义 （P<0.05）,其中5.00 ng/ml组G₀/G₁期细胞由对照组的（49.33±3.25）%升高至（79.47± 2.40）%,S期和G₂/M期细胞由对照组的（28.47±1.59）%和（22.20±2.09）%分别下降至（10.13±3.26）%和（10.40±1.41）%。经CPP处理的MCF-7细胞中p21^WAF1/CIP1 mRNA的表达明显增强,p21^WAF1/CIP1/β-actin光吸度比值与对照组相比明显增高（P<0.05）。免疫细胞化学结果显示,CPP组MCF-7细胞中p21^WAF1/CIP1 蛋白的表达随作用浓度的增加而增强,其中10.00 ng/ml组肿瘤细胞p21^WAF1/CIP1的表达呈强阳性。结论：香加皮杠柳苷（CPP）具有显著的体外抗肿瘤作用,且有效剂量很小,其IC₅₀仅为（4.88±0.16）ng/ml。CPP可使MCF-7细胞发生G₀/G₁期阻滞,并可使细胞周期相关基因p21^WAF1/CIP1的mRNA及蛋白表达增强,提示阻滞细胞周期可能是CPP体外抗肿瘤的作用机制之一。     

CD4 + CD25 + 调节性T细胞与肿瘤免疫治疗

 CD4＋CD25＋调节性T淋巴细胞（regulatory Tcell，Treg）是一类具有独特免疫调节功能的T淋巴细胞亚群，一般占人外周血CD4＋T细胞的5％～15％。近年来，国内外对这类调节性T细胞的研究已从自身免疫耐受、移植免疫逐渐扩展到肿瘤免疫，认为Treg是形成肿瘤免疫耐受的关键成分。     

弥漫大B细胞淋巴瘤外周血CD13+CD4+CD25hi调节性T细胞的表达及其临床意义

目的 探讨CD13+CD4+CD25hi调节性T细胞(Treg细胞)在弥漫大B细胞淋巴瘤(DLBCL)患者外周血中的表达水平及其临床意义.方法 采用流式细胞术检测58例初诊DLBCL患者及30名健康对照者外周血CD13+CD4+CD25hi Treg细胞亚群在Treg细胞中的表达水平,并分析其与各临床指标的关系.结果 初诊DLBCL患者外周血CD13+CD4+CD25hi Treg细胞的表达高于健康对照者,两者差异有统计学意义[(36.37±11.89)%比(9.03±2.10)%,t=7.168,P<0.001].国际预后指数(IPI)评分3~5分的初诊DLBCL患者外周血CD13+CD4+CD25hi Treg细胞表达水平高于0~2分的患者,两者差异有统计学意义[(44.28±10.10)%比(21.51±6.23)%,t=ˉ9.347,P=0.03].Ⅱ、Ⅲ、Ⅳ期DLBCL患者外周血CD13+CD4+CD25hi Treg细胞表达水平分别为(19.48±1.34)%、(33.98±8.03)%、(47.89±8.25)%,三者差异有统计学意义(F=38.363,P<0.001).而不同年龄、性别、乳酸脱氢酶(LDH)水平患者之间外周血CD13+CD4+CD25hi Treg细胞表达水平差异均无统计学意义(均P>0.05).结论 CD13+CD4+CD25hi Treg细胞亚群在DLBCL患者外周血中的表达水平明显升高,并与患者临床分期及预后相关.     

FoxP3mRNA在胃癌患者CD4+CD25+调节性T细胞中的表达及其临床意义

目的探讨胃癌患者体内CD4 CD25 调节性T细胞的含量及FoxP3 mRNA在Treg中的表达情况及其临床意义。方法应用流式细胞术(FCM)测定20例胃癌患者外周血中Treg细胞含量,同时采用RT-PCR技术检测其FoxP3 mRNA的表达情况,并与20例健康志愿者的外周血进行对比研究和统计学分析。结果胃癌患者外周血中Treg细胞占CD4 T细胞总数的(12.76±0.46)%,显著高于健康对照组的(6.81±0.66)%,(P<0.01);FoxP3 mRNA在胃癌患者外周血Treg细胞中呈现高表达(0.84±0.02)%,明显高于其在健康对照组中表达(0.76±0.03)%,(P<0.05)。结论胃癌患者外周血中Treg的数量较正常人明显增高,同时伴随有FoxP3 mRNA高表达,提示FoxP3基因可能对Treg有重要的调节功能,从而影响胃癌病人的抗肿瘤自身免疫功能。     

食管癌患者外周血CD+4 CDHi25 CDLow127 调节性T细胞的表达及其临床意义

 目的　探讨食管癌患者外周血中CD+4 CDHi25 CDLow127 调节性T细胞（Treg细胞）水平的变化及其与临床病理特征的关系。方法　采用流式细胞术检测80例食管癌患者和20名健康志愿者外周血中Treg占CD+4细胞的比例,结合临床及病理资料进行分析。结果　食管癌患者外周血中Treg细胞表达为（5.70±1.96）%,显著高于健康对照组的（3.36±1.14）%（P<0.01）。Treg细胞表达在淋巴结转移阳性患者组为（5.96±1.36）%（n＝40）,显著高于淋巴结转移阴性组的（4.23±1.18）%（n＝30）（P <0.01）。食管癌外周血Treg细胞和TNM分期有着负相关性,TNM分期越晚,Treg细胞表达率越高。结论　Treg细胞在食管癌患者的外周血中表达较健康对照组显著增高,并与临床病理特征存在显著相关性。食管癌发病和分期与免疫功能受抑有密切关系。     

Smad4和Smad7在人脑胶质瘤中的表达及意义

 目的 探讨Smad₄和Smad₇在人脑胶质瘤中的表达及意义。方法 采用免疫组化方法,对临床经过石蜡包埋的30例胶质瘤和8例正常脑组织标本进行定位和定性检测。结果 Smad₄和Smad₇蛋白在胶质瘤中有不同程度的表达,在正常脑组织、低、高级别胶质瘤中Smad₄的阳性表达分别为44．80±16．19,25．81±9．48,6．73±3．71,P<0．05。Smad₇的阳性表达分别为6．69±3．86,18．22±7．84,41．95±17．27,P<0．05。差别均有显著意义。且Smad4与Smad7的表达水平呈负相关,r=-0．82,P<0．01。结论 Smad₄随胶质瘤的病理分级增高阳性表达降低,对胶质瘤的进展有抑制作用。Smad₇则相反,可能参与了胶质瘤的恶性进展。     

CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome

The Cancer Immunoediting concept has provided critical insights suggesting dual functions of immune system during the cancer initiation and development. However, the dynamics and roles of CD4⁺ and CD8⁺ T cells in the pathogenesis of breast cancer remain unclear. Here we utilized two murine breast cancer models (4T1 and E0771) and demonstrated that both CD4⁺ and CD8⁺ T cells were increased and involved in immune responses, but with distinct dynamic trends in breast cancer development. In addition to cell number increases, CD4⁺ T cells changed their dominant subsets from Th1 in the early stages to Treg and Th17 cells in the late stages of the cancer progression. We also analyzed CD4⁺ and CD8⁺ T cell infiltration in primary breast cancer tissues from cancer patients. We observed that CD8⁺ T cells are the key effector cell population mediating effective anti-tumor immunity resulting in better clinical outcomes. In contrast, intra-tumoral CD4⁺ T cells have negative prognostic effects on breast cancer patient outcomes. These studies indicate that CD4⁺ and CD8⁺ T cells have opposing roles in breast cancer progression and outcomes, which provides new insights relevant for the development of effective cancer immunotherapeutic approaches.     

健择联合顺铂化疗对非小细胞肺癌患者外周血CD4~+CD25~+Foxp3~+调节T细胞的影响

目的探讨健择联合顺铂对非小细胞肺癌患者免疫耐受的调控作用。方法38例经病理学或细胞学确诊的NSCLC患者,采用健择、顺铂联合化疗方案,应用流式细胞仪检测化疗前后外周血CD4+CD25+Foxp3+调节T细胞(Treg)占CD4+T细胞的百分率。结果化疗前NSCLC患者外周血CD4+CD25+Foxp3+调节T细胞(Treg)占CD4+T细胞的比率明显高于健康对照组(P<0.05);化疗后NSCLC患者外周血CD4+CD25+Foxp3+调节T细胞(Treg)占CD4+T细胞的百分率较化疗前显著降低(P<0.05);但鳞癌、腺癌及腺鳞癌3组间化疗前、化疗后各项指标之间差异无统计学意义(P>0.05)。结论健择联合顺铂化疗可调控晚期非小细胞肺癌机体的肿瘤免疫耐受,改善患者的免疫功能。     

Phorbol ester effects on splenic lymphocyte composition and cytotoxic T cell activities of SSIN mice: a strain deficient in CD8+ T cells

SSIN mice are considerably more sensitive to the effects of12-O-tetradecanoylphorbol-13-acetate (TPA) in two-stage skincarcinogenesis protocols than are most other strains and stocksof mice. Experiments were performed to determine whether therewas an immunological basis for this sensitivity. SSIN mice werehaplotyped and found to be H-2^q. T cells represented 31% ofthe splenic cellularity of non-treated SSIN mice, but 44% inBALB/c, C57BL/6, B₆C₃F₁ and SENCAR mice. Splenic CD4⁺/CD8⁺ Tcell ratios were 4.2, 2.9, 2.4, 1.8 and 1.7 in SSIN, SENCAR,BALB/c, B₆C₃F₁ and C57BL/6 mice, respectively. The unusuallyhigh ratio in SSIN spleens was the consequence of reductionsin CD8⁺ T cells. The ratio of CD4⁺/CD8⁺ T cells in SSIN thymocyteswas similiar to that measured in the spleen. The splenic cytotoxicT lymphocyte (CTL) activities of the various murine strainsinversely correlated with their splenic CD4⁺/CD8⁺ ratios andtheir sensitivities in two-stage skin carcinogenesis protocols.Repeated in vivo topical treatment of SSIN mice with TPA causedsignificant decreases in splenic T cell contents, but affectedneither the splenic CD4⁺/CD8⁺ T cell ratio nor the developmentof a CTL response upon allogeneic tumor challenge. SSIN micealso had very low splenic natural killer cell activities. Furthermore,relative to the other strains of mice, SSIN mice were poor respondersupon alloantigen challenge in mixed lymphocyte response assays.These findings demonstrate that SSIN mice differ markedly fromother murine stocks and strains in their splenic lymphocytecomposition and in their abilities to mount some MHC-restrictedand non-restricted immunosurveillance processes.     

Skewed immunological balance between Th17 (CD4+IL17A+) and Treg (CD4+CD25+FOXP3+) cells in human oral squamous cell carcinoma

Background

Several studies have documented modulation of Th17 and T regulatory (Treg) cells in various human malignancies which may vary with the type and extent of the disease. However, such data in patients with oral cancer is scarce and hence the current study was designed to elaborate the immunological balance between these two T cell subsets in oral cancer.

Methods and results

We analyzed various T cell subsets in the peripheral blood of 45 oral squamous cell carcinoma (OSCC) patients and 40 healthy volunteers. We found that, compared with the healthy controls, patients had a significantly (p?<?0.0001) higher proportion of both Th17 (CD4⁺IL17A⁺) and Treg (CD4⁺CD25⁺FOXP3⁺) cells, which further showed a reciprocal balance in relation to clinico-pathological parameters in patients. We also detected a circulating CD8⁺ subset of these cells in both patients and healthy controls, although the difference between the two groups was statistically insignificant. Higher frequencies of Th17 cells were found in patients with early stages and without lymph node involvement, while an increased prevalence of Tregs was associated with higher clinical stages and lymph node involvement. Moreover, Th17 cells were quantitatively and positively correlated to CD4⁺T and CD8⁺T cells and inversely correlated with Tregs. Contrarily, Tregs showed a negative association with CD4⁺T and CD8⁺T cells.

Conclusions

Our results suggest an increase in Th17/Tregs ratio in early stages and a decrease in this ratio in higher stages of oral cancer. Such counter regulation of Th17 and Tregs may be a significant prognostic factor in oral cancer patients.     

The prognostic value of peripheral CD4+CD25+ T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cells-cytokine induced killer cells infusion

Objective

This study aimed to assess the prognostic value of CD4⁺CD25⁺ T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy.

Methods

217 patients participated in the follow-up study. CD4⁺CD25⁺ proportion was measured by flow cytometry in peripheral T cells. The median survival was estimated by Kaplan-Meier curve, Log-rank test and Cox hazard proportion regression model, between groups of CD4⁺CD25⁺ proportion more than 5% and less than or equal to 5% in peripheral T cells.

Results

Peripheral CD4⁺CD25⁺ T lymphocytes had not a relationship with progression-free survival. It was featured that above 5% peripheral CD4⁺CD25⁺ proportion of T cells was related with the median overall survival by a shorten of 51 months (p < 0.05) with the HR 1.65 (95%CI 1.04, 2.62). Above 5% CD4⁺CD25⁺proportion of T cells produced the HR to be 1.76 (95%CI 1.07, 2.87) In stage 0-II patients, and 3.59 (95%CI 1.05, 12.29) in triple negative breast cancer patients.

Conclusion

Cellular immunity restoration recovered by adoptive T cell infusions which resulted in less proportion of peripheral CD4⁺CD25⁺T lymphocytes could be a potential prognostic indicator among early stage and triple negative patients.     

卵巢癌患者腹水及外周血CD4+ CD25+调节性T细胞含量及抑制功能的研究

  目的   研究卵巢癌患者腹水及外周血单个核细胞（PBMC）中CD4+ CD25+调节性T细胞（Treg）的表达差异、免疫调节功能及其含量与化疗、复发的关系,探究其在卵巢癌腹腔微环境中发挥免疫调节的具体作用及意义。   方法   采用流式细胞术分别检测27例卵巢癌患者腹水及28例卵巢癌患者PBMC中CD4+ CD25+/CD4+ T细胞百分比,并根据收集标本时患者临床特征进行分组,比较处于初治（PD）、化疗后（AC）及复发（RD）3个阶段卵巢癌患者腹水及PBMC中Treg含量的差异。应用免疫磁珠分选卵巢癌患者腹水及外周血Treg,与经羧基荧光素二醋酸盐琥珀酰亚胺酯（carboxyfluorescein succinimidylester,CFSE）标记的自CD4+CD25- T细胞按不同比例（0:1,1:1,1:2及1:4）共培养,检测Treg免疫抑制功能。   结果   卵巢癌患者腹水中CD4+ CD25+/CD4+ T细胞百分比（28.25±14.06）%较PBMC中（14.6±4.74）%显著增高（P < 0.000 1）。卵巢癌患者PD、AC及RD 3个阶段腹水及PBMC中Treg含量均显示为AC>RD>PD,且均有显著统计学意义（P < 0.000 1）。体外实验结果显示,卵巢癌患者腹水中CD4+ CD25+ Treg可有效抑制CFSE标记的自体CD4+ CD25- T细胞增殖,且抑制功能较外周血显著增强（P < 0.01）。   结论   卵巢癌腹腔微环境中存在CD4+ CD25+Treg,且其含量及免疫抑制功能较外周血PBMC显著增高,提示卵巢癌腹腔内更易发生免疫逃逸作用。卵巢癌患者化疗后及复发阶段腹水及PBMC中CD4+ CD25+ Treg含量均大于原发阶段,提示化疗可能促进卵巢癌患者体内Treg含量升高,而Treg升高可能参与促进肿瘤复发。       

DC-CIK对胃癌合并腹水患者外周血CD4+CD25+调节性T细胞增殖及功能的影响

目的:探讨DC-CIK对胃癌合并腹水患者外周血CD4+CD25+调节性T胞(Treg细胞)比例及功能的影响。方法:60例胃癌合并腹水患者,于输注DC-CIK前1天及DC-CIK治疗结束后1周分别采集外周血。流式细胞术检测外周血Treg细胞的比例,RT-PCR法检测其Foxp3mRNA表达情况;将分选出的Treg细胞和CD4+CD25-T细胞分为单纯Treg细胞组（A组）、1∶1混合培养（B组）、单纯CD4+CD25-细胞组（C组）进行培养,3H-TdR掺入法检测Treg细胞抑制CD4+CD25-细胞增殖的能力。结果:治疗后外周血Treg细胞占CD4+T细胞的比例较疗前显著下降［(6.21±1.37)% vs (9.38±1.06)%,P＜0.05］。治疗后Treg细胞Foxp3mRNA表达水平较治疗前显著下降［(56.18±13.25)% vs (85.26±11.58)%,P＜0.05］。治疗后Treg对CD4+CD25-T细胞抑制增殖能力较治疗前明显下降［(37.31±4.16)% vs (48.92±5.25)%,P＜0.05］。结论:输注DC-CIK免疫治疗,可显著降低胃癌合并腹水患者外周血Treg细胞比例,下调Foxp3mRNA表达水平,降低Treg细胞免疫抑制功能,有利于诱导抗肿瘤免疫效应。     

蛋白酶体抑制剂PS-341 诱导U266 细胞凋亡与胞浆内[Ca 2+]变化的关系

 目的 探讨蛋白酶体抑制剂PS-341（Bortezomib）诱导骨髓瘤细胞株U266细胞凋亡时对其胞浆内[Ca²⁺]（[Ca²⁺]i）的影响。方法 以浓度梯度的PS-341干预U266细胞4h后收集,荧光显微镜观察细胞凋亡,Annexin V-FITC／PI双参数流式细胞术（FCM）检测细胞凋亡,Fluo-3／AM荧光素标记FCM检测[Ca²⁺]i。结果 （1）PS-341作用U266细胞4h后荧光显微镜观察到凋亡细胞数随浓度增加而增多;（2）FCM检测凋亡细胞的比例分别为0．56％、7．71％、19．84％、31．10％、40．72％,与PS-341浓度成正比;（3）PS-341作用后U266细胞[Ca²⁺]i均值分别为403．65nmol／L、418．20nmol／L、378．65nmol／L、356．36nmol／L、349．21nmol／L;（4）PS-341诱导U266细胞凋亡时伴随[Ca²⁺]i的改变,浓度〉50nmol／L时诱导的细胞凋亡伴随[Ca²⁺]i下降。结论 蛋白酶体抑制荆PS-341诱导骨髓瘤细胞凋亡呈浓度依赖性;PS-341浓度〉50nmol／L时下调[Ca²⁺]i,并由此发挥抗骨髓瘤细胞作用。