SCR7对三阴性乳腺癌顺铂化疗的增敏作用研究

Study on the sensitizing effect of SCR7 on cisplatin chemotherapy in triple-negative breast cancer

摘要:

目的 探讨SCR7对三阴性乳腺癌顺铂化疗的增敏作用。方法 选用三阴乳腺癌MDA-MB-231细胞分为空白对照组、10 μmol/L顺铂对照组和联合组（10 μmol/L顺铂+10、20和40 μmol/L SCR7），采用CCK-8法检测细胞活性并计算细胞增殖抑制率；取对数期TNBC MDA-MB-231细胞构建三阴性乳腺癌移植瘤小鼠模型，建模成功后荷瘤裸鼠随机分为对照组、SCR7组，顺铂组、SCR7+顺铂组；饲养24 d后，观察比较各组荷瘤鼠肿瘤质量、瘤体体积的变化，计算肿瘤抑制率；苏木精-伊红（hematoxylin-eosin，HE）染色观察瘤体组织细胞形态学变化；原位末端标记法（in situ end labeling，TUNEL）检测乳腺癌肿瘤组织的凋亡；采用Western blot检测X射线修复交叉互补蛋白1（X-ray repair cross complementing 1，XRCC1）、多聚（ADP核糖）聚合酶1[poly（adp ribose） polymerase 1，PARP1]蛋白表达。结果 联合组细胞增殖抑制率均高于对照组（P<0.05），且随SCR7质量浓度增大呈逐渐升高趋势（P<0.05）。体内动物实验发现：相较于对照组，SCR7组、顺铂组、SCR7+顺铂组中的乳腺癌肿瘤体积、瘤重减小（P<0.05），其肿瘤抑制率分别是32%、40%、81%；SCR7+顺铂组较顺铂组减少更明显（P<0.05），且小鼠体质量与SCR7组、顺铂组相比无明显差异（P>0.05）；HE染色观察干预组肿瘤组织均呈现明显形态学改变，其中SCR7+顺铂组肿瘤细胞退变变化最明显；TUNEL染色显示SCR7+顺铂组肿瘤细胞凋亡最为严重，可见大量红色细胞凋亡；Western blot检测发现，SCR7+顺铂组XRCC1、PARP1蛋白表达均明显低于其他组，差异均有统计学意义（P<0.05）。结论 SCR7在体内外对三阴乳腺癌顺铂化疗均有增敏作用。

Abstract:

Objective To investigate the sensitizing effect of SCR7 on cisplatin chemotherapy in triple-negative breast cancer（TNBC）.Methods MDA-MB-231 cells of TNBC were selected and divided into blank control group，10 μmol/L cisplatin control group and combined group（10 μmol/L cisplatin + 10，20 and 40 μmol/L SCR7）. CCK-8 method was used to detect cell activity and calculate cell proliferation inhibition rate. A TNBC mice model was constructed by using TNBC MDA-MB-231 cells. The nude mice were randomly divided into control group，SCR7 group，cisplatin group and SCR7+cisplatin group. After 24 days of feeding，the changes of mass and tumor volume of tumor-bearing mice in all groups were observed and compared，and the tumor inhibition rate was calculated. Morphological changes of tumor cells were observed by hematoxylin - eosin（HE） staining. The apoptosis of tumor cells was detected by in situ end labeling（TUNEL） method，and the expressions of X-ray repair cross complementing 1（XRCC1） and poly（ADP-ribose） polymerase 1（PARP1） proteins were detected by Western blot.Results The cell proliferation inhibition rate in the combined group was higher than that in the control group（P<0.05），and it wasgradually increased with the increase of SCR7 concentration（P<0.05）. Animal experiments in vivo found：compared with the control group，the tumor volume and tumor weight of breast cancer in SCR7 group，cisplatin group and SCR7+cisplatin group decreased（P<0.05），and the tumor inhibition rates were 32%，40% and 81%，respectively. The SCR7+cisplatin group showed a more significant reduction than SCR7 group and cisplatin group（P<0.05），but there was no significant difference in mouse body weight compared to the cisplatin group（P>0.05）. The tumor tissues in the intervention groups showed obvious morphological changes by HE staining，among which the tumor cells in the SCR7+cisplatin group showed the most obvious degenerative changes. TUNEL staining showed that the tumor cells in the SCR7+cisplatin group had the most serious apoptosis，and a large number of red apoptotic cells were seened. Western blotting showed that the protein expressions of XRCC1 and PARP1 in SCR7+cisplatin group were significantly lower than those in other groups，and the differences were statistically significant（P<0.05）.Conclusion SCR7 has sensitizing effect on cisplatin chemotherapy for TNBC in vivo and in vitro.