SD大鼠胰腺癌模型及其DNA损伤修复蛋白和癌干细胞标记蛋白在诱癌中的作用
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摘要
第一部分SD大鼠胰腺癌模型建立及其病理学研究
目的应用二甲基苯荓蒽(DMBA)置入大鼠胰腺实质内建立胰腺癌模型(A组),同时应用曲古霉素A (TSA)设立干预组(B组),探讨该模型的意义及TSA的抑瘤作用。
方法切开SD大鼠胰腺被膜及部分胰实质,深约1mm,A组和B组均置入9mgDMBA;C组(正常对照组)大鼠除未置入DMBA外余同A组,B组大鼠每周腹腔注射1μg/ml TSA生理盐水溶液1ml。3-5个月处死大鼠,大体和显微镜下观察胰腺及胰腺外主要器官有无肿瘤形成及其病理学改变。
结果(1)3-5个月A组大鼠胰腺癌发生率为48.7%(18/37),其中病理学类型包括17例胰腺导管腺癌(高分化6例、中分化7例和低分化4例)和1例胰腺纤维肉瘤；3个月组胰腺癌发生率(2/7)低于4个月组(4/10)和5个月组(12/20),但无统计学差异(P>0.05)。(2)3-5个月B组大鼠胰腺癌发生率为33.3%(12/36),其中病理学类型包括11例胰腺导管腺癌(高分化6例、中分化4例和低分化1例)和1例胰腺纤维肉瘤；3个月组胰腺癌发生率(1/6)低于4个月组(3/10)和5个月组(8/20),但无统计学差异(P>0.05)。(3)A组胰腺癌发生率高于B组,但无统计学差异(P>0.05)；(4)A组胰腺导管癌肿块直径显著大于B组(P<0.05)。(5)A组和B组非癌胰腺导管上皮呈增生及不典型增生改变,A组非癌胰腺导管上皮呈轻度不典型增生5例(5/19,26.3%)和中至重度不典型增生10例(10/19,52.6%),B组非癌胰腺导管上皮呈轻度不典型增生10例(10/24,41.6%)及中至重度不典型增生8例(8/24,33.3%),但两组之间无显著差异(P>0.05)。(6)C组胰腺及A、B两组胰腺外主要脏器均未见明显肉眼和镜下病理学改变。
结论较大剂量DMBA直接置入胰实质内可在短期内获得较高的胰腺癌发生率,为胰腺导管腺癌较理想的动物模型；TSA可抑制大鼠胰腺癌的发生和生长。
第二部分DNA损伤修复蛋白在大鼠胰腺癌和非癌胰腺组织中表达及意义
目的研究4种DNA损伤修复蛋白(ERCC1, MGMT, hMSH2和hMLH1)在DMBA诱导的大鼠胰腺癌和非癌胰腺组织中表达水平及其在DMBA诱癌过程中的作用。
方法大鼠胰腺癌和非癌胰腺组织及C组正常胰腺组织经4%甲醛固定后常规制作石蜡包埋切片,ERCC1, MGMT, hMSH2和hMLH1染色方法为EnvisionTM二步免疫组化法。
结果(1)A组3-5个月癌发生率为48.7%(18/37),17例为胰腺导管腺癌和1例为胰腺纤维肉瘤；B组3-5个月癌发生率为33.3%(12/36),11例为胰腺导管腺癌和1例为胰腺纤维肉瘤；A组胰腺导管腺癌肿块最大径均值大于B组胰腺导管腺癌(P<0.05)。(2)A组+B组胰腺导管腺癌组织中ERCC1, MGMT, hMSH2和hMLH1表达阳性率均明显地低于A组+B组非癌胰腺组织(P<0.05或P<0.01)；A组胰腺导管腺癌ERCC1, MGMT, hMSH2和hMLH1表达阳性率低于A组非癌胰腺组织,但无明显统计学差异(P>0.05)；B组胰腺导管腺癌ERCC1, MGMT, hMSH2和]hMLH1表达阳性率均明显低于B组非癌胰腺组织,有明显统计学差异(P<0.05)；A组和B组非癌胰腺组织ERCC1, MGMT, hMSH2和(或)hMLH1表达阴性者胰腺导管上皮均呈轻度、中度和重度不典型增生。
结论较大剂量DMBA置入胰实质内可在短期内获得较高胰腺癌发生率；TSA能抑制胰腺癌的发生和生长；在DMBA诱导胰腺癌发生发展过程中DNA损伤修复蛋白失活可能起较重要作用。
第三部分大鼠胰腺癌和非癌胰腺组织癌干细胞标记物表达研究
目的建立Sprague-Dawely (SD)大鼠胰腺癌模型,研究胰腺癌发生过程中癌干细胞标记物(PSCA、Oct-4、CD24和CD44V6)表达状况及其意义。
方法将二甲基苯荓蒽(dimethylbenzanthracene, DMBA)直接置入胰腺被膜下胰实质内设立胰腺癌模型组(A组),另一组同样置入DMBA并每周腹腔注射曲古霉素(trichostatin,TSA)设立为干预组(B组),A组和B组鼠于3-5个月内处死,正常对照组(C组)于第5个月处死；肉眼检查及HE染色观察胰腺癌发生情况,PSCA、Oct-4、CD24和CD44V6染色方法均为EnvisionTM免疫组化法。
结果(1)A组3-5个月癌发生率为48.7%(18/37),17例为胰腺导管腺癌,1例为纤维肉瘤；B组3-5个月癌发生率为33.3%(12/36),11例为胰腺导管腺癌,1例为纤维肉瘤；A组胰腺癌最大径均值大于B组(P<0.05)；C组胰腺及A组、B组胰腺外主要脏器均无明显病理改变；(2)A组±B组胰腺导管腺癌PSCA、Oct-4、CD24和CD44V6表达阳性率明显高于A组±B组非癌胰腺组织(P<0.01),C组胰腺PSCA、Oct-4、CD24和CD44V6表达均阴性；A组胰腺导管腺癌和B组胰腺导管腺癌PSCA、Oct-4、CD24和CD44V6表达阳性率分别明显高于A组非癌胰腺组织和B组非癌胰腺组织(P<0.05)。
结论较大剂量DMBA置入胰实质内可在短期内获得较高的胰腺癌发生率,TSA能干预胰腺癌的发生和生长；在DMBA诱导胰腺癌发生发展过程中癌干细胞及其标记物可能起着较重要的作用。
PartyⅠEstablishment of a model for pancreatic cancer in Sprague-Dawely rat and its pathological study
Objective To establish a model of pancreatic cancer induced by dimethylbenzanthracene(DMBA) in Sprague-Dawely rats and investigate the pathological changes and inhibitive effect of trichostatin A (TSA) on the carcinogenesis and growth of pancreatic cancer.
Methods The membrane and panrenchyma (about 1mm depth) of rat pancreas was opened to implant a higher dose (9 mg) of DMBA in group A and group B rats, and then the incision was closed with interrupted sutures. The rats of group B was then treated with 1 ml TSA saline solution (1μg/ml) via ip weekly. The pancreas and other main organs of extra-pancreas of rats sacrificed within 3-5 months were studied by macrograph and under-microscopy.
Results (1) The prevalence of pancreatic cancer among rats of group A within 3-5 months was 48.7%(18/37), pathological types including 17 cases with pancreatic ductal adenocarcinoma and 1 case with fibrosarcoma. The prevalence of pancreatic cancer for five months was higher than that for three or four months, but no satistical difference was found(P>0.05). (2) The prevalence of pancreatic cancer among rats of group B within 3-5 months was 33.3%(12/36), pathological types including 11 cases with pancreatic ductal adenocarcinoma and 1 case with fibrosarcoma. The prevalence of pancreatic cancer for five months was higher than that for three or four month, but no significance was found (P>0.05). (3) The prevalence of pancreatic cancer in group A was higher than that in group B, but no satastical difference was found (P> 0.05). (4) The maximal diameter of neoplastic mass was significantly higher in group A than that in group B (P<0.05). (5) Non-cancerous pancreatic tissues in group A and group B showed the hyperplasia to atypical-hyperplasia of ductal epitheli of pancreas.19 cases out of non-cancerous pancreatic tissues in group A included 5 cases of mild-atypical hyperplasia and 10 cases of moderately to severely-atypical hyperplasia of ductal epithelial cells.24 cases out of non-cancerous pancreatic tissuer in group B included 10 cases of mild-atypical hyperplasia and 8 cases of moderately to severely-atypical hyperplasia of ductal epithelial cells. But no satastical difference compared group A with group B was found (P>0.05). (6) The pancreas of group c and other main organs of group A and group B had no pathological changes of macrograph and under-microscopy.
Conclusions Higher dose of DMBA implanted directly into the parenchyma of pancreas could obtain an ideal pancreatic cancer model with high incidence in a short time. TSA might have an inhibitive effect on the carcinogenesis and growth of rat pancreatic ductal adenocarcinoma.
Party II Expression of repair proteins of DNA damage and their significances in pancreatic cancer and non-cancerous pancreatic tissues of Sprague-Dawely(SD) rats
Objective To establish a model of pancreatic cancer induced by dimethylbenzantracene (DMBA) in SD rats, and detect the expressive levels of repair proteins of DNA damage(MGMT, ERCC1, hMSH2 and hMLH1) and their effect on carcinogenesis of rat pancreas.
Methods DMBA was directly implanted into the parenchyma of pancreas in rats (group A+ group B), The rats of group B were treated with 1ml TSA saline solution (1μg/ml) via ip weekly. The carcinogenesis of rats executed within 3～5 months in group A and group B was observed by macrography and under microscopy. Meanwhile, the rats in the control group (group C) were executed in 5 months. The En VisionTM immunohistochemistry was used for assaying the expressive levels of MGMT, ERCC1, hMSH2 and hMLH1 in conventional paraffin-embedded sections from above pancreatic specimens.
Results (1) The incidence of pancreatic cancer in group A within 3～5 months was 48.7%(18/37), including 17 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The incidence of pancreatic cancer in group B was 33.3%(12/36), including 11 cases of pancreatic ductal adenocarcinoma and 1 cases of fibrosarcoma. The maximal diameter of tumor mass in group A was larger than that in group B (P<0.05). No pathological changes were found in pancreas of group C and other main organs of group A and group B. (2) The positive rates of MGMT, ERCC1, hMSH2 and hMLH1 were significantly lower in ductal adenocarcinoma of group A+group B than those in non-cancerous pancreatic tissues of group A+group B(P<0.05 or P<0.01). No statistial differences were found among the expression rates of MGMT, ERCC1, hMSH2 and hMLH1 in ductal adenocarcinoma and non-cancerous pancreatic tissues of group A(P>0.05). The positive rates of MGMT, ERCC1, hMSH2 and hMLH1 were significantly lower in ductal adenocarcinoma of group B than those in non-cancerous pancreatic tissues of group B(P≤0.05). Pancreas of group C was positive expression of MGMT, ERCC1, hMSH2 and hMLH1.2 cases of fibrosarcoma was negative expression of MGMT, ERCC1, hMSH2 and hMLH1.
Conclusions DMBA directly implanted into the parenchyma of pancreas can obtain an ideal pancreatic cancer model with high incidence in a short time. TSA may have an inhibitive effect on the carcinogenesis in rat pancreas. The repair proteins of DNA damage, including MGMT, ERCC1, hMSH2 and hMLH1, might have loss expressions and important effects on the carcinogenesis induced by DMBA in rat pancreas.
Party III Expression of cancer stem cell markers and its significances in pancreatic cancer and non-canerous pancreatic tissues of Sprague-Dawely(SD)rats
Objective To establish a model of pancreectic cancer induced by dimethylbenzanthracene(DMBA) in SD rats, and detect the expressive levels of cancer stem cell markers (PSCA,Oct-4, CD24 and CD44V6)in the carcinogenesis and progression and their significances.
Methods DMBA was directly implanted into the parenchyma of pancreas in rats (group A+B). The rats of group B were treated with 1ml TSA saline solution (1μg/me)via ip weekly.The carcinogenesis of rats executed within 3-5 months in group A and group B were observed by HE staining and macrography. Meanwhile, the rats in the control (group C)were executed in 5 months. The En VisionTM immunohistochemistry was used for assaying the expressive levels of PSCA, Oct-4 CD24, and CD44V6.
Results (1)The incidence of pancreatic cancer in group A within 3-5 months was 48.7%(18/37),including 17 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The incidence of pancreatic cancer in group B was 33.3%(12/36), including 11 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The maxial diameter of tumor mass in group A was larger than that in group B(P<005). No pathological changes were found in pancreas of group C and other main organ of group A and group B. (2)The positive rates of PSCA,Oct-4、CD24 and CD44V6 were significantly higher in pancreatic ductal adenacarcinoma of group A+ group B than those in non-cancerous pancreatic tissues of group A+ group B (P<0.01). The positive rates of PSCA, Oct-4, CD24 and CD44V6 were significantly higher in pancreatic cancer of group A or group B than those in non-cancerous tissues corresponding group A or group B (P<0.01). No positive case of PSCA, Oct-4, CD24 and CD44V6 was found the pancreatic tissues of group C.
Conclusions DMBA directly implanted into the parenchyma of parcreas can obtain an ideal pancreatic cancer model with high incidence in a short time. TSA may have an inhibitive effect on the carcinogenesis and growth of pancreatic cancer in rats. Cancer stem cells and their markers(PSCA, Oct4, CD24, CD44V6)might have important effects on the carcinogenesis and progression of rat pancreatic cancer induced by DMBA.
目的应用二甲基苯荓蒽(DMBA)置入大鼠胰腺实质内建立胰腺癌模型(A组),同时应用曲古霉素A (TSA)设立干预组(B组),探讨该模型的意义及TSA的抑瘤作用。
方法切开SD大鼠胰腺被膜及部分胰实质,深约1mm,A组和B组均置入9mgDMBA;C组(正常对照组)大鼠除未置入DMBA外余同A组,B组大鼠每周腹腔注射1μg/ml TSA生理盐水溶液1ml。3-5个月处死大鼠,大体和显微镜下观察胰腺及胰腺外主要器官有无肿瘤形成及其病理学改变。
结果(1)3-5个月A组大鼠胰腺癌发生率为48.7%(18/37),其中病理学类型包括17例胰腺导管腺癌(高分化6例、中分化7例和低分化4例)和1例胰腺纤维肉瘤；3个月组胰腺癌发生率(2/7)低于4个月组(4/10)和5个月组(12/20),但无统计学差异(P>0.05)。(2)3-5个月B组大鼠胰腺癌发生率为33.3%(12/36),其中病理学类型包括11例胰腺导管腺癌(高分化6例、中分化4例和低分化1例)和1例胰腺纤维肉瘤；3个月组胰腺癌发生率(1/6)低于4个月组(3/10)和5个月组(8/20),但无统计学差异(P>0.05)。(3)A组胰腺癌发生率高于B组,但无统计学差异(P>0.05)；(4)A组胰腺导管癌肿块直径显著大于B组(P<0.05)。(5)A组和B组非癌胰腺导管上皮呈增生及不典型增生改变,A组非癌胰腺导管上皮呈轻度不典型增生5例(5/19,26.3%)和中至重度不典型增生10例(10/19,52.6%),B组非癌胰腺导管上皮呈轻度不典型增生10例(10/24,41.6%)及中至重度不典型增生8例(8/24,33.3%),但两组之间无显著差异(P>0.05)。(6)C组胰腺及A、B两组胰腺外主要脏器均未见明显肉眼和镜下病理学改变。
结论较大剂量DMBA直接置入胰实质内可在短期内获得较高的胰腺癌发生率,为胰腺导管腺癌较理想的动物模型；TSA可抑制大鼠胰腺癌的发生和生长。
第二部分DNA损伤修复蛋白在大鼠胰腺癌和非癌胰腺组织中表达及意义
目的研究4种DNA损伤修复蛋白(ERCC1, MGMT, hMSH2和hMLH1)在DMBA诱导的大鼠胰腺癌和非癌胰腺组织中表达水平及其在DMBA诱癌过程中的作用。
方法大鼠胰腺癌和非癌胰腺组织及C组正常胰腺组织经4%甲醛固定后常规制作石蜡包埋切片,ERCC1, MGMT, hMSH2和hMLH1染色方法为EnvisionTM二步免疫组化法。
结果(1)A组3-5个月癌发生率为48.7%(18/37),17例为胰腺导管腺癌和1例为胰腺纤维肉瘤；B组3-5个月癌发生率为33.3%(12/36),11例为胰腺导管腺癌和1例为胰腺纤维肉瘤；A组胰腺导管腺癌肿块最大径均值大于B组胰腺导管腺癌(P<0.05)。(2)A组+B组胰腺导管腺癌组织中ERCC1, MGMT, hMSH2和hMLH1表达阳性率均明显地低于A组+B组非癌胰腺组织(P<0.05或P<0.01)；A组胰腺导管腺癌ERCC1, MGMT, hMSH2和hMLH1表达阳性率低于A组非癌胰腺组织,但无明显统计学差异(P>0.05)；B组胰腺导管腺癌ERCC1, MGMT, hMSH2和]hMLH1表达阳性率均明显低于B组非癌胰腺组织,有明显统计学差异(P<0.05)；A组和B组非癌胰腺组织ERCC1, MGMT, hMSH2和(或)hMLH1表达阴性者胰腺导管上皮均呈轻度、中度和重度不典型增生。
结论较大剂量DMBA置入胰实质内可在短期内获得较高胰腺癌发生率；TSA能抑制胰腺癌的发生和生长；在DMBA诱导胰腺癌发生发展过程中DNA损伤修复蛋白失活可能起较重要作用。
第三部分大鼠胰腺癌和非癌胰腺组织癌干细胞标记物表达研究
目的建立Sprague-Dawely (SD)大鼠胰腺癌模型,研究胰腺癌发生过程中癌干细胞标记物(PSCA、Oct-4、CD24和CD44V6)表达状况及其意义。
方法将二甲基苯荓蒽(dimethylbenzanthracene, DMBA)直接置入胰腺被膜下胰实质内设立胰腺癌模型组(A组),另一组同样置入DMBA并每周腹腔注射曲古霉素(trichostatin,TSA)设立为干预组(B组),A组和B组鼠于3-5个月内处死,正常对照组(C组)于第5个月处死；肉眼检查及HE染色观察胰腺癌发生情况,PSCA、Oct-4、CD24和CD44V6染色方法均为EnvisionTM免疫组化法。
结果(1)A组3-5个月癌发生率为48.7%(18/37),17例为胰腺导管腺癌,1例为纤维肉瘤；B组3-5个月癌发生率为33.3%(12/36),11例为胰腺导管腺癌,1例为纤维肉瘤；A组胰腺癌最大径均值大于B组(P<0.05)；C组胰腺及A组、B组胰腺外主要脏器均无明显病理改变；(2)A组±B组胰腺导管腺癌PSCA、Oct-4、CD24和CD44V6表达阳性率明显高于A组±B组非癌胰腺组织(P<0.01),C组胰腺PSCA、Oct-4、CD24和CD44V6表达均阴性；A组胰腺导管腺癌和B组胰腺导管腺癌PSCA、Oct-4、CD24和CD44V6表达阳性率分别明显高于A组非癌胰腺组织和B组非癌胰腺组织(P<0.05)。
结论较大剂量DMBA置入胰实质内可在短期内获得较高的胰腺癌发生率,TSA能干预胰腺癌的发生和生长；在DMBA诱导胰腺癌发生发展过程中癌干细胞及其标记物可能起着较重要的作用。
PartyⅠEstablishment of a model for pancreatic cancer in Sprague-Dawely rat and its pathological study
Objective To establish a model of pancreatic cancer induced by dimethylbenzanthracene(DMBA) in Sprague-Dawely rats and investigate the pathological changes and inhibitive effect of trichostatin A (TSA) on the carcinogenesis and growth of pancreatic cancer.
Methods The membrane and panrenchyma (about 1mm depth) of rat pancreas was opened to implant a higher dose (9 mg) of DMBA in group A and group B rats, and then the incision was closed with interrupted sutures. The rats of group B was then treated with 1 ml TSA saline solution (1μg/ml) via ip weekly. The pancreas and other main organs of extra-pancreas of rats sacrificed within 3-5 months were studied by macrograph and under-microscopy.
Results (1) The prevalence of pancreatic cancer among rats of group A within 3-5 months was 48.7%(18/37), pathological types including 17 cases with pancreatic ductal adenocarcinoma and 1 case with fibrosarcoma. The prevalence of pancreatic cancer for five months was higher than that for three or four months, but no satistical difference was found(P>0.05). (2) The prevalence of pancreatic cancer among rats of group B within 3-5 months was 33.3%(12/36), pathological types including 11 cases with pancreatic ductal adenocarcinoma and 1 case with fibrosarcoma. The prevalence of pancreatic cancer for five months was higher than that for three or four month, but no significance was found (P>0.05). (3) The prevalence of pancreatic cancer in group A was higher than that in group B, but no satastical difference was found (P> 0.05). (4) The maximal diameter of neoplastic mass was significantly higher in group A than that in group B (P<0.05). (5) Non-cancerous pancreatic tissues in group A and group B showed the hyperplasia to atypical-hyperplasia of ductal epitheli of pancreas.19 cases out of non-cancerous pancreatic tissues in group A included 5 cases of mild-atypical hyperplasia and 10 cases of moderately to severely-atypical hyperplasia of ductal epithelial cells.24 cases out of non-cancerous pancreatic tissuer in group B included 10 cases of mild-atypical hyperplasia and 8 cases of moderately to severely-atypical hyperplasia of ductal epithelial cells. But no satastical difference compared group A with group B was found (P>0.05). (6) The pancreas of group c and other main organs of group A and group B had no pathological changes of macrograph and under-microscopy.
Conclusions Higher dose of DMBA implanted directly into the parenchyma of pancreas could obtain an ideal pancreatic cancer model with high incidence in a short time. TSA might have an inhibitive effect on the carcinogenesis and growth of rat pancreatic ductal adenocarcinoma.
Party II Expression of repair proteins of DNA damage and their significances in pancreatic cancer and non-cancerous pancreatic tissues of Sprague-Dawely(SD) rats
Objective To establish a model of pancreatic cancer induced by dimethylbenzantracene (DMBA) in SD rats, and detect the expressive levels of repair proteins of DNA damage(MGMT, ERCC1, hMSH2 and hMLH1) and their effect on carcinogenesis of rat pancreas.
Methods DMBA was directly implanted into the parenchyma of pancreas in rats (group A+ group B), The rats of group B were treated with 1ml TSA saline solution (1μg/ml) via ip weekly. The carcinogenesis of rats executed within 3～5 months in group A and group B was observed by macrography and under microscopy. Meanwhile, the rats in the control group (group C) were executed in 5 months. The En VisionTM immunohistochemistry was used for assaying the expressive levels of MGMT, ERCC1, hMSH2 and hMLH1 in conventional paraffin-embedded sections from above pancreatic specimens.
Results (1) The incidence of pancreatic cancer in group A within 3～5 months was 48.7%(18/37), including 17 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The incidence of pancreatic cancer in group B was 33.3%(12/36), including 11 cases of pancreatic ductal adenocarcinoma and 1 cases of fibrosarcoma. The maximal diameter of tumor mass in group A was larger than that in group B (P<0.05). No pathological changes were found in pancreas of group C and other main organs of group A and group B. (2) The positive rates of MGMT, ERCC1, hMSH2 and hMLH1 were significantly lower in ductal adenocarcinoma of group A+group B than those in non-cancerous pancreatic tissues of group A+group B(P<0.05 or P<0.01). No statistial differences were found among the expression rates of MGMT, ERCC1, hMSH2 and hMLH1 in ductal adenocarcinoma and non-cancerous pancreatic tissues of group A(P>0.05). The positive rates of MGMT, ERCC1, hMSH2 and hMLH1 were significantly lower in ductal adenocarcinoma of group B than those in non-cancerous pancreatic tissues of group B(P≤0.05). Pancreas of group C was positive expression of MGMT, ERCC1, hMSH2 and hMLH1.2 cases of fibrosarcoma was negative expression of MGMT, ERCC1, hMSH2 and hMLH1.
Conclusions DMBA directly implanted into the parenchyma of pancreas can obtain an ideal pancreatic cancer model with high incidence in a short time. TSA may have an inhibitive effect on the carcinogenesis in rat pancreas. The repair proteins of DNA damage, including MGMT, ERCC1, hMSH2 and hMLH1, might have loss expressions and important effects on the carcinogenesis induced by DMBA in rat pancreas.
Party III Expression of cancer stem cell markers and its significances in pancreatic cancer and non-canerous pancreatic tissues of Sprague-Dawely(SD)rats
Objective To establish a model of pancreectic cancer induced by dimethylbenzanthracene(DMBA) in SD rats, and detect the expressive levels of cancer stem cell markers (PSCA,Oct-4, CD24 and CD44V6)in the carcinogenesis and progression and their significances.
Methods DMBA was directly implanted into the parenchyma of pancreas in rats (group A+B). The rats of group B were treated with 1ml TSA saline solution (1μg/me)via ip weekly.The carcinogenesis of rats executed within 3-5 months in group A and group B were observed by HE staining and macrography. Meanwhile, the rats in the control (group C)were executed in 5 months. The En VisionTM immunohistochemistry was used for assaying the expressive levels of PSCA, Oct-4 CD24, and CD44V6.
Results (1)The incidence of pancreatic cancer in group A within 3-5 months was 48.7%(18/37),including 17 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The incidence of pancreatic cancer in group B was 33.3%(12/36), including 11 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The maxial diameter of tumor mass in group A was larger than that in group B(P<005). No pathological changes were found in pancreas of group C and other main organ of group A and group B. (2)The positive rates of PSCA,Oct-4、CD24 and CD44V6 were significantly higher in pancreatic ductal adenacarcinoma of group A+ group B than those in non-cancerous pancreatic tissues of group A+ group B (P<0.01). The positive rates of PSCA, Oct-4, CD24 and CD44V6 were significantly higher in pancreatic cancer of group A or group B than those in non-cancerous tissues corresponding group A or group B (P<0.01). No positive case of PSCA, Oct-4, CD24 and CD44V6 was found the pancreatic tissues of group C.
Conclusions DMBA directly implanted into the parenchyma of parcreas can obtain an ideal pancreatic cancer model with high incidence in a short time. TSA may have an inhibitive effect on the carcinogenesis and growth of pancreatic cancer in rats. Cancer stem cells and their markers(PSCA, Oct4, CD24, CD44V6)might have important effects on the carcinogenesis and progression of rat pancreatic cancer induced by DMBA.
引文
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