【作者】 王玉栋； 刘巍； 纪芝民； 张志刚； 吕雅蕾； 王淑琴；

【Author】 Wang Yu-Dong Liu Wei Ji Zhi-Min Zhang Zhi-Gang Lu Ya-Lei Wang Shu-Qin Department of Medical Oncology, the Fourth Hospital of Hebel Medical University, Shyiazhuang 050011, P.R.China,

【机构】 河北医科大学第四医院暨河北省肿瘤医院肿瘤内科；

【摘要】 目的:研究不同化疗方案对PCNA和Bcl-2的影响,探讨新辅助化疗与乳腺癌预后指标的关系和二者评价乳腺癌化疗效果的价值,为推行个体化治疗寻找新的依据和思路。方法:I建立MCF-7乳腺癌荷瘤裸鼠模型,共48只, 随机分为5个化疗组和1个对照组,每组8只。5个化疗组按2／3LD10剂量分别腹腔注射或口服给予CMF、CAF、NP、 TP和Xeloda方案化疗,对照组腹腔注射生理盐水。2．观察裸鼠体重,瘤重和抑瘤率,分析联合化疗对MCF-7乳腺癌移植瘤的杀伤和抑制作用,3．通过免疫组织化学方法分析5 个化疗组和对照组乳腺癌组织PCNA和Bcl-2表达情况,并通过HE染色评价病理学疗效,分析化疗后PCNA和Bcl- 2表达水平与病理学疗效分级的关系。4．采用SPSS10．0统计学软件,各项参数值之间用单因素方差分析、x2检验、 spearman等级相关分析。以a=0．05作为统计学检验的显著性水准。结果:1,5个化疗组裸鼠体重分别为17．40± 1．69g、14．33±1．37g、15．39±1．67g、16．36±1．95g和 14．59±0．90g均明显低于对照组22．25±0．81g,均有显著性差异(p<0．05)。移植瘤重量分别为213．00± 230．04mg、307．78±231．89mg、193．55±91．73mg、 151．91±60．86mg和113．47±83．69mg均显著小于对照组的1258．75±216．27mg,均有显著性差异(p<0．05)。抑瘤率分别为83．1％、75．5％、84．6％、87．9％、91．0％。2、5个化疗组瘤组织PCNA表达LI值分别是58．38±9．49％、 60．38±9．58％、37．50±6．76％、43．63±5．53％和50．00 ±5．56％,明显低于对照组的79．5±9．49％,均有显著性差异(p<0．05)。且NP、TP和Xeloda组显著低于CMF、 CAF组(p<0．05)。5个化疗组Bcl-2蛋白表达LI值分别为 32．00±3．74％、32．50±7．78％、38．38±4．72％、40．13 ±7．28％和36．25±4．71％,均高于对照组的25．75± 8．65％,且CAF、NP、TP和Xeloda与对照组有显著性差异(p<0．05)。且TP组显著高于CMF、CAF组(p<0．05)。 3．PCNA表达在三个病理疗效分级间有显著性差异(x 2=12．061,p<0．05),且呈显著正相关(r=0．540,p<0．05)。 Bcl-2表达在三个病理疗效分级间有显著性差异(x2= 12．542,p<0．05),呈负相关趋势,但无统计学意义(r= -0．306,p>0．05)。结论:1、5个化疗方案均对裸鼠MCF- 7乳腺癌移植瘤有明显抑瘤作用,且可降低肿瘤组织PCNA 表达,降低肿瘤的增殖活性,并可增强Bcl-2蛋白的表达, 抑制肿瘤细胞的凋亡,建立细胞增殖和凋亡之间的平衡。2．化疗后PCNA表达与病理学疗效呈显著正相关,而化疗后 Bcl-2表达与病理学疗效呈负相关趋势。3．化疗后PCNA和 Bcl-2表达水平可作为评价乳腺癌化疗效果的参考指标,且可尝试作为制定个体化治疗方案参考指标。更多还原

【Abstract】 Objective: To investigate the effects of various chemotherapy regimens on the expression of PCNA and Bcl-2 of breast cancer . To assess relationships between neoadjuvant chemotherapy and breast cancer prognostic factors, and to evaluate the use of two markers as predictive factors for the response of different chemotherapy regimens. Ultimately, the aim of this study was to look for new evidences to direct clinical ChemoSelect, and to carry out individualized treatment Methods: Forty-eight nude mice models of human breast cancer xenograft (MCF-7) were established, and then were randomly divided into control and 5 chemotherapy groups. Among 5 chemotherapy groups (each group, n =8), mice were treated intraperitoneallyoral by 5 combination chemotherapy regimens (CMF, CAF, NP, TP, Xeloda) respectively at two-third LD10 (dose lethal to 10% of the mice). Control animals (n = 8) were administered intraperitoneally with normal saline. The body weight and transplanted tumor weight were observed, the inhibition rate of tumor growth was calculated. The antitumor activities of various chemotherapy regimens on nude mice bearing tumor were analyzed. The pathological features of transplanted tumor were studied by HE stain under microscope and the pathohistology therapeutic effects were evaluated. The expression of Bcl-2 and PCNA was comparatively studied in chemotherapy group and control group by SP immuno-histochemical method. The correlations between the expression of Bcl-2 and PCNA and the pathohistology therapeutic effects were analyzed. The data were presented with mean and standard deviation, analyzed with one ANOVA test, Chi-square test, and spearman rank correlation with Statistic software of SPSS 10.0 edition. Results: Body weight of nude mice in 5 chemotherapy groups (17.40 ± 1.69g, 14.33 ±1.37g, 15.39 ±1.67g, 16.36 ±1.95g and 14.59 ±0.90g ) were significantly lower than that of the control (22.25 ±0.81g)(p<0.05), and tumor weight of nude mice in 5 chemotherapy groups (213.00 ±230.04mg, 307.78 ±231.89mg, 193.55 ±91.73mgl51.91 ±60.86mg and 113.47 ±83.69mg) were significantly lower than that of the control (1258.75 ±216.27mg) (p<0.05). The inhibition rate of tumor growth were 83.1%, 75.5%, 84.6%, 87.9% and 91.0%, respectively. 2 Immunohistochemical studies : LI (labeling index) value of PCNA in 5 chemotherapy group (58.38 ±9.49% 、60.38 ±9.58% 、37.50 ±6.76%. 43.63 ±5.53% and 50.00 ±5.56%) was significantly lower than that of normal control (79.5 ±9.49%) (p<0.05). Moreover, PI value of PCNA in NP , TP and Xeloda group was significantly lower than that of CMF and CAF group (p<0.05). LI value of Bcl-2 in 5 chemotherapy group (32.00 ±3.74%,32.50 ±7.78%,38.38 ±4.72%,40.13 ±7.28% and 36.25 ±4.71%) was higher than that of normal control (25.75 ±8.65%), and there were significant statistical differences between CAF, NP, TP, Xeloda and the control (p<0.05). Moreover, LI value of Bcl-2 in TP group was significantly higher than th更多还原