新辅助化疗对ⅡB期骨肉瘤细胞Cyclin D1、Bcl-2、PCNA和P-gp表达的影响

目的探讨新辅助化疗对骨肉瘤组织中细胞周期素D1(CyclinD1)、Bcl-2、增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)和P-糖蛋白(P-glycoprotein,P-gp)表达的影响,及与肿瘤细胞坏死率(tumorcellnecrosisrate,TC-NR)的关系。方法应用免疫组织化学技术检测化疗前后23例骨肉瘤组织标本中CyclinD1、Bcl-2、PCNA和P-gp的表达,并计算TCNR。结果新辅助化疗前CyclinD1、Bcl-2、PCNA和P-gp的阳性表达率分别为73.9%(17/23)、69.6%(16/23)、91.3%(21/23)和21.7%(5/23),新辅助化疗后的阳性表达率分别为52.2%(12/23)、34.8%(8/23)、43.5%(10/23)和56.5%(13/23)。化疗后,骨肉瘤组织中Bcl-2、PCNA的表达低于化疗前,P值分别为0.039和0.034;P-gp高于化疗前,P=0.021;CyclinD1的表达差别无统计学意义,P=0.180。化疗前CyclinD1、Bcl-2、PCNA和P-gp的表达与TCNR无相关性,P值分别为0.155、0.371、1.000和0.640;而化疗后Bcl-2、PCNA和P-gp的表达与TCNR呈负相关,P值分别为0.009、0.012和0.015;CyclinD1的表达与TCNR无相关性,P=0.100。结论新辅助化疗可能通过抑制肿瘤细胞的增殖和促进肿瘤细胞的凋亡达到杀灭骨肉瘤细胞的目的;同时,由于MDR的过度表达,增加骨肉瘤细胞对化疗药物的耐药性。检测化疗前CyclinD1、Bcl-2、PCNA和P-gp在肿瘤细胞中的表达尚难以预测骨肉瘤的化疗疗效。

Influence of neoadjuvant chemotherapy on expression of Cyclin D1 ,Bcl-2, PCNA and P-gp in Ⅱ B osteosarcoma cells

OBJECTIVE:To study the influence of neoadjuvant chemotherapy on expression of Cyclin D1,Bcl-2,PCNA and P-gp in osteosarcoma cells and the relationship between the expression and TCNR. METHODS: With immunohistochemical technology,the expression of Cyclin D1,Bcl-2,PCNA and P-gp were determined in 23 cases of osteosarcoma and TCNR was calculated. RESULTS: The positive expression rate of Cyclin D1,Bcl-2, PCNA and P-gp before neoadjavant chemotherapy was 73.9%(17/23), 69.6%(16/23), 91.3%(21/23) and 21.7%(5/23), respectively. The positive expression rate after neoadjuvant chemotherapy was 52.2%(12/23), 34.8%(8/23), 43.5%(10/23) and 56.5%(13/23), respectively. The positive expression rate of Bcl-2,PCNA after chemotherapy was much lower than that beforechemotherapy, P=0.039,0.034. After chemotherapy,the expression rate of P-gp was higher, P=0.021 and there was no signficant difference in the expression of Cyclin D1, P=0.180. No relation existed between the expression of Cyclin D1,Bcl-2,PCNA,P-gp and TCNR before chemotherapy, P=0.155,0.371,1.000 and 0.640. There was negative correlation between the expression of Bcl-2,PCNA,P-gp and TCNR (P=0.009,0.012 and 0.015),and no relationship existed between the Cyclin D1 and the TCNR (P=0.100) after chemotherapy. CONCLUSION: Chemotherapy could inhibit proliferation and induce apoptosis on osteosarcoma cells. At the same time, due to the overexpression of the P-gp,the drug resistance of the osteosarcoma cells was increased. The determination of Cyclin D1,Bcl-2,PCNA and P-gp before chemotherapy could not predict the curative effect of the chemotherapy.