目的观察破壁灵芝孢子(GLS)粉对人乳腺癌MCF-7细胞移植瘤生长增殖作用和TMSG-1 m RNA表达的影响。方法建立人乳腺癌MCF-7细胞裸鼠移植瘤模型,把30只成瘤裸鼠随机分为五组,每组6只,分别为不同剂量破壁GLS组(1.5、3、4.5 g/kg)、磷酰胺(C...目的观察破壁灵芝孢子(GLS)粉对人乳腺癌MCF-7细胞移植瘤生长增殖作用和TMSG-1 m RNA表达的影响。方法建立人乳腺癌MCF-7细胞裸鼠移植瘤模型,把30只成瘤裸鼠随机分为五组,每组6只,分别为不同剂量破壁GLS组(1.5、3、4.5 g/kg)、磷酰胺(CTX)模型组、生理盐水组。用药4 w后观察破壁灵芝孢子粉对裸鼠移植瘤体积、瘤重的影响,并计算抑制率;用流式细胞术(FCM)测定细胞增殖周期和细胞凋亡水平;用半定量RT-PCR检测肿瘤组织中TMSG-1 m RNA的表达。结果与对照组比较,中剂量和高剂量破壁GLS组(3、4.5 g/kg)、模型组的移植瘤重瘤体积与对照组比较显著减少(P<0.05),中剂量、高剂量破壁GLS组和模型组的肿瘤抑制率分别为36.7%、44.5%、54.2%;用药4 w后,癌细胞S期和G2/M期细胞所占比例下降,相应的G0/G1期细胞增加,药物抑制了细胞的正常增殖,凋亡实验显示药物组细胞凋亡率增加,药物组总体凋亡率高于对照组(P<0.05或P<0.01);RT-PCR结果,破壁GLS组(1.5、3、4.5 g/kg)可使TMSG-1 m RNA表达明显上调,与生理盐水组比较显著增加(P<0.05或P<0.01)。结论破壁GLS粉具有抑制肿瘤细胞增殖、诱导细胞凋亡的作用,同时上调MCF-7细胞裸鼠移植瘤组织中TMSG-1 m RNA的表达发挥潜在的抗肿瘤细胞转移的作用。展开更多
Objective: To investigate the antitumor activity of different combination regimens to human breast cancer xeno-graft (MCF-7) transplanted in nude mice and the effects on the expression of PCNA, and to evaluate the val...Objective: To investigate the antitumor activity of different combination regimens to human breast cancer xeno-graft (MCF-7) transplanted in nude mice and the effects on the expression of PCNA, and to evaluate the value of PCNA as predictive factor for the response of chemotherapy and individualized treatment. Methods: (1) 88 nude mice models of human breast cancer xenograft (MCF-7) were established, and then were randomly divided into control group and 10 chemotherapy groups (each group, n = 8). Among them, the mice of 5 chemotherapy groups were treated intraperitoneally/orally by 5 com-bination chemotherapy regimens (CMF, CAF, NP, TP, Xeloda) respectively at 1/3 LD10 dosage schedule (dose lethal to 10% of the mice), and that in another 5 chemotherapy groups were treated at 2/3 LD10 dosage schedule. Control animals were administered intraperitoneally with normal saline. (2) The body weight of nude mice and transplanted tumor growth were ob-served and recorded, then inhibition rate of tumor growth was calculated. (3) The pathological features of transplanted tumor were studied under microscope. The expression of proliferating cell nuclear antigen (PCNA) was comparatively studied in chemotherapy group and control group by SP immunohistochemical method and flow cytometry analysis. Results: (1) Body weight, tumor weight and inhibition rate of tumor growth of athymic mice bearing cancer: Body weights and tumor weights of nude mice in every 2/3 LD10 chemotherapy group were significantly lower than those of the control group (P < 0.05), and the inhibition rates of tumor growth were 83.1%, 75.5%, 84.6%, 87.9% and 91.0%, respectively. Body weights of athymic mice in every 1/3 LD10 chemotherapy group were lower than that of the control (P < 0.05). The results showed that the 2/3 LD10 chemotherapy groups could reflect the effect of combination chemotherapy on the nude mice and the clinical dependability was better. So the data of 2/3 LD10 chemotherapy groups were appropriated for successive study. (2) Immunohistochemical studies: The expressions of PCNA in every chemotherapy group were significantly lower than that of the control (P < 0.05). Moreover, the expression of PCNA in NP group was significantly lower than those of CMF, CAF, TP and Xeloda groups (P < 0.05), while the expressions of TP and Xeloda groups were significantly lower than those of CMF and CAF groups (P < 0.05). (3) FCM analysis: FI values of PCNA in every chemotherapy group were significantly lower than that of the control (P < 0.05). FI values of PCNA in TP and Xeloda groups were significantly lower than those of CMF and CAF groups (P < 0.05), while the value of NP group was significantly lower than that of CMF group (P < 0.05). (4) Relationship between PCNA expression and pathologic response: The expression of PCNA was significantly correlated with pathological therapeutic response of transplanted breast carcinoma (P = 0.001). Conclusion: In vivo chemosensitivity testing with 2/3 LD10 dosage combinations in nude mice bearing cancer can reflect the effects of chemotherapeutics and affects of organism exactly. Various chemotherapy regimens all can decrease the expression of PCNA in breast cancer. The PCNA can be regarded as the factor to judge the response to chemotherapy, and it become possibly one of the prospective factors in the selection of chemotherapy regimen and play a rule in individualized therapy in the clinic.展开更多
文摘目的观察破壁灵芝孢子(GLS)粉对人乳腺癌MCF-7细胞移植瘤生长增殖作用和TMSG-1 m RNA表达的影响。方法建立人乳腺癌MCF-7细胞裸鼠移植瘤模型,把30只成瘤裸鼠随机分为五组,每组6只,分别为不同剂量破壁GLS组(1.5、3、4.5 g/kg)、磷酰胺(CTX)模型组、生理盐水组。用药4 w后观察破壁灵芝孢子粉对裸鼠移植瘤体积、瘤重的影响,并计算抑制率;用流式细胞术(FCM)测定细胞增殖周期和细胞凋亡水平;用半定量RT-PCR检测肿瘤组织中TMSG-1 m RNA的表达。结果与对照组比较,中剂量和高剂量破壁GLS组(3、4.5 g/kg)、模型组的移植瘤重瘤体积与对照组比较显著减少(P<0.05),中剂量、高剂量破壁GLS组和模型组的肿瘤抑制率分别为36.7%、44.5%、54.2%;用药4 w后,癌细胞S期和G2/M期细胞所占比例下降,相应的G0/G1期细胞增加,药物抑制了细胞的正常增殖,凋亡实验显示药物组细胞凋亡率增加,药物组总体凋亡率高于对照组(P<0.05或P<0.01);RT-PCR结果,破壁GLS组(1.5、3、4.5 g/kg)可使TMSG-1 m RNA表达明显上调,与生理盐水组比较显著增加(P<0.05或P<0.01)。结论破壁GLS粉具有抑制肿瘤细胞增殖、诱导细胞凋亡的作用,同时上调MCF-7细胞裸鼠移植瘤组织中TMSG-1 m RNA的表达发挥潜在的抗肿瘤细胞转移的作用。
文摘Objective: To investigate the antitumor activity of different combination regimens to human breast cancer xeno-graft (MCF-7) transplanted in nude mice and the effects on the expression of PCNA, and to evaluate the value of PCNA as predictive factor for the response of chemotherapy and individualized treatment. Methods: (1) 88 nude mice models of human breast cancer xenograft (MCF-7) were established, and then were randomly divided into control group and 10 chemotherapy groups (each group, n = 8). Among them, the mice of 5 chemotherapy groups were treated intraperitoneally/orally by 5 com-bination chemotherapy regimens (CMF, CAF, NP, TP, Xeloda) respectively at 1/3 LD10 dosage schedule (dose lethal to 10% of the mice), and that in another 5 chemotherapy groups were treated at 2/3 LD10 dosage schedule. Control animals were administered intraperitoneally with normal saline. (2) The body weight of nude mice and transplanted tumor growth were ob-served and recorded, then inhibition rate of tumor growth was calculated. (3) The pathological features of transplanted tumor were studied under microscope. The expression of proliferating cell nuclear antigen (PCNA) was comparatively studied in chemotherapy group and control group by SP immunohistochemical method and flow cytometry analysis. Results: (1) Body weight, tumor weight and inhibition rate of tumor growth of athymic mice bearing cancer: Body weights and tumor weights of nude mice in every 2/3 LD10 chemotherapy group were significantly lower than those of the control group (P < 0.05), and the inhibition rates of tumor growth were 83.1%, 75.5%, 84.6%, 87.9% and 91.0%, respectively. Body weights of athymic mice in every 1/3 LD10 chemotherapy group were lower than that of the control (P < 0.05). The results showed that the 2/3 LD10 chemotherapy groups could reflect the effect of combination chemotherapy on the nude mice and the clinical dependability was better. So the data of 2/3 LD10 chemotherapy groups were appropriated for successive study. (2) Immunohistochemical studies: The expressions of PCNA in every chemotherapy group were significantly lower than that of the control (P < 0.05). Moreover, the expression of PCNA in NP group was significantly lower than those of CMF, CAF, TP and Xeloda groups (P < 0.05), while the expressions of TP and Xeloda groups were significantly lower than those of CMF and CAF groups (P < 0.05). (3) FCM analysis: FI values of PCNA in every chemotherapy group were significantly lower than that of the control (P < 0.05). FI values of PCNA in TP and Xeloda groups were significantly lower than those of CMF and CAF groups (P < 0.05), while the value of NP group was significantly lower than that of CMF group (P < 0.05). (4) Relationship between PCNA expression and pathologic response: The expression of PCNA was significantly correlated with pathological therapeutic response of transplanted breast carcinoma (P = 0.001). Conclusion: In vivo chemosensitivity testing with 2/3 LD10 dosage combinations in nude mice bearing cancer can reflect the effects of chemotherapeutics and affects of organism exactly. Various chemotherapy regimens all can decrease the expression of PCNA in breast cancer. The PCNA can be regarded as the factor to judge the response to chemotherapy, and it become possibly one of the prospective factors in the selection of chemotherapy regimen and play a rule in individualized therapy in the clinic.
