抗人EGFR/抗CD3双功能抗体的制备、检测及对胃癌细胞毒性作用的实验研究

目的探讨抗EGFR/抗CD3双功能抗体体外对胃癌细胞的杀伤能力,为临床应用该抗体治疗胃癌打下实验基础。方法采取化学偶联法合成抗EGFR/抗CD3双功能抗体并使用间接细胞免疫荧光法检测该抗体的功能。通过细胞结合率检测及MTT杀伤实验检测其对胃癌细胞结合及杀伤的能力并与单纯的EGFR单抗和CD3单抗比较。结果抗EGFR/抗CD3双功能抗体联合效应细胞与胃癌细胞株SGC7901结合率显著高于两组单抗对照组(P<0.05);MTT细胞杀伤实验结果提示:抗EGFR/抗CD3双功能抗体组对胃癌细胞株SGC7901杀伤率显著高两组单抗对照组(P<0.05)。结论初步的体外实验显示由化学偶联法合成的抗EG-FR/抗CD3双功能抗体可能对胃癌有一定的治疗作用,具有进一步研究的价值。     

EGFR单抗联合CIK细胞治疗胃癌的实验研究

背景:单克隆抗体靶向药物和细胞免疫治疗在恶性肿瘤的治疗中越来越显现出巨大的潜力,但二者联合应用在胃癌治疗中的作用尚未明确。目的:通过体外和体内实验初步探讨表皮生长因子受体(EGFR)单抗(西妥昔单抗)联合细胞因子诱导的杀伤细胞(CIK细胞)对胃癌的治疗作用。方法:经免疫细胞化学方法证实人胃腺癌细胞株SGC7901高表达EGFR后,观察EGFR单抗对CIK细胞与SGC7901细胞结合率的影响。设置EGFR单抗联合CIK细胞组、单纯CIK细胞组和单纯EGFR单抗组,以MTT法检测各组对SGC7901细胞的杀伤率,应用裸鼠移植瘤模型观察各组抑瘤率。结果:EGFR单抗未能显著提高CIK细胞与SGC7901细胞的结合率。EGFR单抗联合CIK细胞对SGC7901细胞的杀伤率和裸鼠移植瘤抑制率显著高于两者单用(P0.05)。结论:EGFR单抗与CIK细胞联合对胃癌的疗效较两者单用显著提高。     

EGFR单抗联合GIK细胞治疗胃癌的实验研究

单克隆抗体靶向药物和细胞免疫治疗在恶性肿瘤的治疗中越来越显现出巨大的潜力,但二者联合应用在胃癌治疗中的作用尚未明确。目的：通过体外和体内实验初步探讨表皮生长因子受体（EGFR）单抗（西妥昔单抗）联合细胞因子诱导的杀伤细胞（CIK细胞）对胃癌的治疗作用。方法：经免疫细胞化学方法证实人胃腺癌细胞株SGC7901高表达EGFR后．观察EGFR单抗对CIK细胞与SGC7901细胞结合率的影响。设置EGFR单抗联合CIK细胞组、单纯CIK细胞组和单纯EGFR单抗组,以MTT法检测各组对SGC7901细胞的杀伤率．应用裸鼠移植瘤模型观察各组抑瘤率。结果：EGFR单抗未能显著提高CIK细胞与SGC7901细胞的结合率。EGFR单抗联合CIK细胞对SGC7901细胞的杀伤率和裸鼠移植瘤抑制率显著高于两者单用（P〈0．05）。结论：EGFR单抗与CIK细胞联合对胃癌的疗效较两者单用显著提高．     

增强CD16分子表达对CIK细胞杀伤胃癌细胞能力影响的研究

目的 初步验证增强表达CD16分子的CIK细胞联合EGFR单克隆抗体在体外对胃癌细胞的杀伤作用.探讨其治疗胃癌的临床应用前景.方法 将CD16基因插入载体pcDNA3.1构建PC-CD16真核表达载体,脂质体瞬时转染CIK细胞增强其CD16表达建立CD16高表达的CIK-CD16细胞系.该细胞系联合EGFR单克隆抗体进行51Cr杀伤实验检测其与胃癌SGC7901细胞结合及杀伤能力并与普通CIK细胞比较.使用流式细胞仪法检测治疗后肿瘤细胞周期与凋亡情况变化.结果 51Cr细胞杀伤实验结果提示:CIK-CD16细胞联合EGFR单克隆抗体对胃癌细胞株SGC7901杀伤率显著高于各对照组(P＜0.05).CIK-CD16细胞联合EGFR单克隆抗体处理后肿瘤细胞凋亡率上升.结论 初步的体外实验显示,增强CD16表达的CIK细胞联合EGFR单克隆抗体可有效增强免疫效应细胞对胃癌的杀伤作用,具有潜在的临床应用价值.     

抗CD133/CD3双特异性抗体装载的CIK细胞对高表达CD133结直肠癌细胞杀伤效应的探讨

目的 探讨抗CD133/CD3双特异性抗体装载的CIK（BsAb-CIK）细胞对高表达CD133结直肠癌细胞的杀伤效应。方法 通过化学偶联制备抗CD133和抗CD3的双特异性抗体。利用CCK8试剂盒检测CIK和BsAb-CIK对高表达CD133结直肠癌细胞系（SW620和HT29）和低表达CD133结直肠癌CIK和BsAb-CIK细胞系（LOVO）的杀伤能力,并检测培养上清中细胞因子分泌水平。构建裸鼠皮下移植瘤模型,随后从腹腔进行CIK和BsAb-CIK细胞输注,1个月后取瘤称重并统计组间肿瘤生长的差异。结果 在不同效靶比条件下（1∶5,1∶10,1∶20）,BsAb-CIK细胞对高表达CD133的结直肠癌细胞系SW620和HT29的杀伤作用均明显强于单纯CIK组（P＜0.05）,而BsAb-CIK细胞对低表达CD133的结直肠癌细胞系LOVO的杀伤作用与单纯CIK组相比,没有显著性差异（P＞0.05）。BsAb-CIK细胞INF-γ分泌明显高于单纯CIK组（P＜0.05）。与单纯CIK治疗组比较,BsAb-CIK细胞对移植瘤的生长抑制作用更加显著（P＜0.05）。结论 BsAb-CIK细胞能够有效杀伤高表达CD133的结直肠癌细胞。     

CD28单抗对γδT细胞增殖和杀伤胃癌细胞的增强作用

目的探讨CD28单克隆抗体对人外周血γδT细胞体外增殖及杀伤胃癌BCG823、SGC7901细胞活性的影响。方法分离健康人外周血单个核细胞(PBMC),分别在有或无CD28单抗(20μg/ml)参与的条件下,加入到含帕米膦酸、IL-2的RPMI1640完全培养基中诱导培养γδT细胞。在培养的第10天用台盼蓝染色计数细胞;采用流式细胞术检测各组γδT细胞的纯度及其穿孔素、颗粒酶B和CD107a的表达;用CCK-8试剂盒检测γδT细胞对胃癌细胞BCG823的体外杀伤效应。结果在诱导培养10d后,两组γδT细胞纯度均达到70%以上,与无CD28单抗对照组相比,CD28单抗组γδT细胞纯度显著高于对照组;CD28单抗组γδT细胞扩增倍数、穿孔素、颗粒酶B和CD107a的表达及对胃癌细胞BCG823和SGC7901的杀伤活性均显著高于无CD28单抗对照组。结论 CD28共刺激能增强γδT细胞增殖并通过上调穿孔素和颗粒酶B的表达增强其抗肿瘤活性。     

细小病毒H-1非结构蛋白NS1基因对人胃癌细胞的抑制作用研究

前期研究表明细小病毒H-1（H-1PV）对胃癌细胞生长具有一定抑制作用,非结构蛋白NSl可能是其细胞毒作用的效应蛋白。胃癌细胞CD44^＋群体中可能含有肿瘤干细胞。目的：探讨H-1PV非结构蛋白NSl基因对不同分化程度的人胃癌细胞的影响。方法：以双酶切和质粒测序鉴定真核表达质粒pcDNA3．1-NSl,采用脂质体法将重组质粒转染高分化胃癌MKN28细胞、中分化胃癌SGC7901细胞和低分化胃癌MKN45细胞,并设置空质粒转染对照。G418筛选稳定转染的细胞克隆．以RT-PCR法检测NSl基因表达、裸鼠体内成瘤实验检测NSl基因对不同分化程度胃癌细胞的作用．流式细胞术分析CD44表达。结果：重组质粒pcDNA3．1-NSl转染的三种胃癌细胞均稳定表达NSl基因。以10^6／300μl浓度的肿瘤细胞皮下接种裸鼠3周后,MKN28细胞空质粒转染组和重组质粒pcDNA3．1-NSl转染组均观察到肿瘤生长;SGC7901、MKN45细胞空质粒转染组形成瘤体,而重组质粒pcDNA3．1-NSl转染组未见瘤体。转染重组质粒pcDNA3．1-NSl后,MKN28细胞不表达CD44,SGC7901和MKN45细胞CD44表达明显降低。结论：H-1PV非结构蛋白NSl基因表达对中低分化的胃癌细胞有较好的抗肿瘤活性．可能与其降低胃癌干细胞表型CD44的表达有关。     

树突状细胞联合细胞因子诱导的杀伤细胞对胃癌细胞杀伤作用

目的探讨树突状细胞联合细胞因子诱导的杀伤细胞对胃癌细胞的杀伤作用。方法采用胃癌患者自身血液中单个核细胞(peripheral blood mononuclear cells,PBMC),经体外诱导分别扩增出DC和CIK细胞,二者共同培养后,利用MTT法检测DC细胞联合CIK细胞体外杀伤人胃癌细胞株(MNK-45、MNK-28、SG-7901)的活性。结果DC与CIK细胞共培养后得到的细胞群高表达CD3 CD56 ,平均值达到(56.74±7.63)%。通过彼此相互作用诱导出的细胞群体对胃癌细胞株MNK-45、MNK-28、SG-7901有杀伤作用,且杀伤活性随着效靶比的增加而增强。结论DC与CIK细胞共培养后有很强的增殖能力,对胃癌细胞具有杀伤活性,且其杀伤作用与胃癌细胞类型无相关性。     

CIK联合紫杉醇对胃癌细胞株SGC-7901的杀伤作用观察

目的观察由细胞因子诱导的杀伤细胞（CIK）联合紫杉醇对胃癌细胞株SGC-7901的杀伤作用。方法将健康人外周血单核细胞（PBMC）在体外诱导形成CIK。取SGC-7901,分别加入CIK、紫杉醇、CIK＋紫杉醇培养,采用MTT法分别检测各组细胞的杀伤率。结果5μg/ml的紫杉醇作用于SGC-7901细胞4 h后,分别加入效靶比为10∶1和20∶1的CIK细胞作用24 h,SGC-7901杀伤效率明显高于单用紫杉醇及单用CIK时的杀伤率,P均〈0.01。结论CIK联合紫杉醇对胃癌细胞株SGC-7901的杀伤作用明显增强。     

miR-29通过调节抗凋亡蛋白Mcl-1表达参与胃癌细胞多药耐药的发生

目的研究miR-29在胃癌多药耐药细胞株[SGC7901/长春新碱(vincristine,VCR)及SGC7901/阿霉素(adriamycin,ADR)]及其亲本细胞(SGC7901)中的表达差异,探讨其在胃癌多药耐药发生中的作用及可能机制.方法 qRT-PCR检测miR-29在不同胃癌细胞系中的表达差异,通过细胞转染调控miR-29的表达水平,MTT法检测不同化疗药物对转染后胃癌细胞的IC50值变化;流式细胞术检测细胞凋亡及周期变化;并应用Western blot、双荧光素酶报告基因实验等方法探讨其可能机制.结果 SGC7901/VCR及SGC7901/ADR细胞中miR-29家族(miR-29a/b/c)相对表达量均显著低于其亲本细胞SGC7901(P0.05);MTT实验表明,下调miR-29表达后SGC7901细胞对不同化疗药物的IC50值显著增高(P0.05);而上调miR-29表达后SGC7901/VCR及SGC7901/ADR细胞对不同化疗药物的IC50值则显著降低(P0.05);流式细胞术检测结果显示,miR-29表达变化可显著改变5-氟尿嘧啶诱导胃癌细胞的凋亡水平(P0.05);Western blot、双荧光素酶报告基因实验等证实髓细胞白血病因子-1(myeloid cell leukemia-1,Mcl-1)是miR-29直接调控靶基因.结论 miR-29表达下调是人胃癌细胞多药耐药发生的机制之一,其可能与负性调控抗凋亡蛋白Mcl-1表达有关.     

A bispecific antibody enhances cytokine-induced killer-mediated cytolysis of autologous acute myeloid leukemia cells

An anti-CD3 Fab' x anti-CD13 Fab' bispecific antibody (BsAb) was generated. This BsAb reacted with both CD3+ T cells and CD13+ acute myeloid leukemia (AML) cells. We investigated whether cytokine- stimulated peripheral blood mononuclear cells (PBMC) could lyse patient AML cells after addition of the BsAb. When interleukin-2 (IL-2)- stimulated PBMC were assayed for their cytotoxicity against 51Cr- labeled allogeneic and autologous CD13+ AML cells, their activity was markedly enhanced by the addition of the BsAb. PBMC stimulated with IL- 2 plus anti-CD3 monoclonal antibody (MoAb) showed higher proliferative ability and higher cytotoxicity if this was expressed as lytic units per culture. IL-7-stimulated PBMC also exhibited enhanced cytotoxicity against CD13+ AML cells after addition of the BsAb. Ultrastructurally, CD13+ AML cells incubated with IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb showed apoptotic morphologic changes. A colony assay for AML blast progenitors showed that the colony formation of CD13+ AML cells was inhibited by the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC, and that this inhibition was further enhanced by the addition of the BsAb. A colony assay for normal bone marrow progenitor cells showed that the addition of autologous IL-2 plus anti- CD3 MoAb-stimulated PBMC and the BsAb inhibited the formation of granulocyte-macrophage colonies and mixed-cell colonies. However, the degree of inhibition was smaller than that for the AML blast colonies. Taken together, these findings suggest that this BsAb may be useful for ex vivo purging of CD13+ AML cells in autologous bone marrow transplantation.     

Potentiation of lysis of leukaemia cells by a bispecific antibody to CD33 and CD16 (FcγRIII) expressed by human natural killer (NK) cells

Bispecific antibodies recognizing tumour-associated antigens and trigger molecules expressed on immune effector cells have been shown to redirect cytotoxicity of several types of peripheral blood cells against relevant tumour targets. Among various effector cells, natural killer (NK) cells appear to play a role in defence against leukaemia. Here we report the successful chemical conjugation of monoclonal antibodies to CD33 and CD16 to create a bispecific antibody (BsAb 251x3G8). This bispecific antibody is capable of augmenting the killing of otherwise resistant leukaemia cells by peripheral blood lymphocytes (PBL), purified resting NK (R-NK) cells, and activated NK (A-NK) cells. BsAb 251x3G8 may play a role in the therapy of acute myeloid leukaemia (AML) through redirecting the cytotoxic activity of endogenous or adoptively transferred NK cells.     

胃癌细胞对细小病毒H-1敏感性差异的实验研究

目的 探讨不同胃癌细胞株对细小病毒细胞毒作用的敏感性差异及可能的机制。方法共选用HGC27(未分化)、BGC823(未分化)、MKN45(低分化)、AGS(低分化)、SGC7901(中分化)和MKN28(高分化)等6株不同分化状态的胃癌细胞株，用流式细胞仪分析其各自的细胞周期，H-1病毒感染后采用MTT方法检测不同胃癌细胞株对其细胞毒作用的敏感性差异，用RT-PCR来检测H-1病毒中的非结构蛋白基因(NS-1)在6株不同胃癌细胞中的表达。结果 HGC27、BGC823、MKN45、AGS、SGC7901和MKN28等不同分化状态细胞株中，S期细胞的比率分别为24．72％，30．15％，27．10％，29．03％，31．82％和33．73％。其中HGC27细胞对H-1病毒的细胞毒作用敏感；SGC7901细胞其次；MKN45、AGS细胞对H-1病毒的细胞毒作用中等敏感；MKN28细胞对H-1病毒的细胞毒作用不敏感；而BGC823则对H-1病毒的细胞毒作用抵抗。病毒NS-1的mRNA在HGC27、BGC823、MKN45和SGC7901等细胞中的表达水平较高，而在AGS和MKN28中的表达水平却较低。结论 H-1病毒的细胞毒作用在不同的胃癌细胞株中的差异显著。总体上，与高分化细胞株MKN28细胞相比，分化差的细胞对细小病毒H-1的细胞毒作用敏感性增加。其机制至少部分与分化差细胞中病毒NS-1蛋白的产生和积聚能力增高相关。未分化的BGC823细胞对H-1病毒的细胞毒作用抵抗，进一步证实并非所有的肿瘤细胞都对细小病毒的溶胞性作用敏感。     

Investigation of the sensitivities of distinct gastric cancer cells to parvovirus H‐1 induced cytotoxicity

OBJECTIVE: To investigate the sensitivities of distinct gastric cancer cells to parvovirus H‐1 induced cytotoxicity and the possible mechanism(s). METHODS: There were six distinct differentiated gastric cancer cell lines: HGC27 (undifferentiated), BGC823 (undifferentiated), MKN45 (poorly differentiated), AGS (poorly differentiated), SGC7901 (moderately differentiated) and MKN28 (well differentiated). The cell cycle distributions were measured by flow cytometry and the differential sensitivities of the six distinct gastric cancer cells after H‐1 virus infection were detected by MTT assay. RT‐PCR was used to detect viral NS1 gene expression in all six gastric cancer cell lines. RESULTS: The S phase ratios of HGC27, BGC823, MKN45, AGS, SGC7901 and MKN28 were 24.72%, 30.15%, 27.10%, 29.03%, 31.82% and 33.73%, respectively. HGC27 cells were sensitive to H‐1 virus induced cytotoxicity, followed by SGC7901 cells. MKN45 and AGS cells were moderately sensitive and MKN28 cells were insensitive. However, BGC823 cells were resistant to H‐1 virus induced cytotoxicity. The expressions of viral NS1 were higher in HGC27, BGC823, MKN45 and SGC7901 cells, and lower in AGS and MKN28 cells. CONCLUSIONS: The sensitivities of the distinct gastric cancer cells to H‐1 virus induced cytotoxicity were markedly different. In general, the poorly differentiated cells showed an enhanced sensitivity to H‐1 virus attack compared with well‐differentiated ones. The enhanced sensitivity of poorly versus well‐differentiated gastric cancer cells to H‐1 virus is related in part to the enhanced capacity of the former for NS1 protein production and accumulation. The undifferentiated BGC823 cells were resistant to H‐1 virus triggered cytotoxicity. It may further verify that not all tumor cells are sensitive to H‐1 virus lytic effects.     

&beta;-elemene enhances the radiosensitivity of gastric cancer cells by inhibiting Pak1 activation

AIM: To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms. METHODS: SGC7901, MKN45, MKN28, N87, and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death, respectively. A proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation (IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1 (Pak1) to target Pak1 signaling. Protein levels of PAK1IP1 (p21-activated protein kinase-interacting protein 1), total Pak1 (t-Pak1), phospho-Pak1 (T423), phospho-ERK1/2 (Thr202/Tyr204), and cleaved caspase-3 (17 kDa) were assessed by western blotting. RESULTS: MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally, β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45 (10.4% ± 0.9% vs 34.8% ± 2.8%, P < 0.05) and SGC7901 (11.6% ± 0.9% vs 46.7% ± 5.2%, P < 0.05) human gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Through iTRAQ analysis and western blot validation, we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1 (T423) and phospho-ERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1 (T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition, IPA-3 increased radiation-induced cell death in MKN45 (13.4% ± 0.3% vs 26.6% ± 1.0%, P < 0.05) and SGC7901 (16.0% ± 0.6% vs 37.3% ± 1.7%, P < 0.05) gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation. CONCLUSION: This is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells, and that the mechanism involves inhibition of Pak1 signaling.     

The sensitivity of digestive tract tumor cells to As2O3 is associated with the inherent cellular level of reactive oxygen species

AIM: To explore the correlation of the inherent cellular ROS level with the susceptibility of the digestive tract tumor cells to apoptosis inducted by As2O3. METHODS: Two gastric carcinoma cell lines, SGC7901 and MKN45, and two esophageal carcinoma cell lines, EC/CUHK1(alternatively named EC1.71) and EC1867 with low concentration(2 micromol x L(-1))of As2O3 were cultured espectly, which confirmed the difference in apoptosis susceptibility between SGC7901 and MKN45, and between EC/CUHK1 and EC1867. The cells were incubated with dihydrogenrhodamine123 (DHR123), used as a ROS capture in absence of As2O3.The fluorescent intensity of rhodamine123, which was the product of cellular oxidation of DHR123, was detected by flow cytometry, and ROS was measured. RESULTS: Apoptosis induced by a low concentration of As2O3 was more readily to occur in SGC7901(22.4%+/-2.4%) and EC/CUHK1(27.0%+/-2.9%) than in MKN45(2.1%+/-0.5%) and EC1867(0.8%+/-0.5%).In other words, SGC7901 was more sensitive than MKN45 to As2O3, meanwhile EC/CUHK1 was more sensitive than EC1867 to As2O3. The level of inherent cellular ROS in SGC7901(650+/-37) was higher than that in MKN45(507+/-22)(P<0.01), and the level of inherent cellular ROS in EC/CUHK1(462+/-17) was higher than that in EC1867(187+/-12)(P<0.01).CONCLUSIONS: The cellular sensitivity to apoptosis induced by As2O3 is associated with the difference in cellular ROS level. The inherent ROS level might determinate the apoptotic sensitivity of tumor cells to As2O3.     

HCTB006联合5-FU对胃癌细胞系MKN28、7901的作用及其机制

目的:探讨肿瘤坏死因子相关诱导配体受体(DR5)的单克隆抗体HCTB006联合5-FU对人胃癌细胞系7901、MKN28的作用以及机制.方法:用ATPlite法检测HBCT006单药组、5-FU单药组及两药物合用对胃癌细胞存活率的影响,研究两者之间的关系;采用流式细胞技术检测胃癌细胞系7901以及MKN28表面DR5的表达水平;Westernblot检测上述3组用药后胃癌细胞内XIAP,caspase3的变化.结果:胃癌细胞系7901、MKN28对HCTB006不敏感;5-FU对二者的增殖抑制作用具有时间以及浓度依赖效应;联合用药组具有很好的协同抑制胃癌细胞系增殖的效果,且具有浓度依赖效应,与给药次序无关.流式细胞技术检测胃癌细胞系7901,MKN28表面死亡受体DR5的表达依次为:93.8%以及87.7%.免疫迹印结果表明,联合用药组可以引发胃癌细胞内凋亡抑制蛋白XIAP的降解,激活最终凋亡执行蛋白caspase3,引起细胞死亡.结论:HTB006与5-FU联合应用具有协同杀伤胃癌细胞的作用.胃癌细胞7901、MKN28对于HCTB006的敏感程度与细胞表面DR5的表达量不相关;联合用药作用机制可能与细胞内抑制凋亡蛋白XIAP降解有关.