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富含miR-30a的牛初乳组分通过抑制癌细胞自噬促进顺铂化疗的肿瘤消亡
引用本文:邹珍友,汪 洋,丁寒莹,吴临平,陈淑美,蒋 挺,国 芳,张鹤云,陈 熹,张骑鹏,曾科,张辰宇. 富含miR-30a的牛初乳组分通过抑制癌细胞自噬促进顺铂化疗的肿瘤消亡[J]. 生物化学与生物物理进展, 2012, 39(11): 1099-1108
作者姓名:邹珍友  汪 洋  丁寒莹  吴临平  陈淑美  蒋 挺  国 芳  张鹤云  陈 熹  张骑鹏  曾科  张辰宇
作者单位:江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093,江苏小分子核糖核酸工程研究中心,南京大学生命科学学院医药生物技术国家重点实验室,南京 210093
基金项目:国家重点基础研究发展计划(973)(2012CB517603, 2011CB504803863)和国家自然科学基金(90813035)资助项目
摘    要:本实验首次发现牛初乳中富含miR-30a.取牛初乳中富含miR-30a的组分处理用顺铂化疗的癌细胞,能显著地抑制癌细胞自噬,促进癌细胞凋亡:单独使用顺铂化疗18 h的癌细胞凋亡率为12.5%,而化疗的同时施加富含miR-30a的牛初乳组分18 h后癌细胞凋亡率为56.5%.用这种富含miR-30a的牛初乳组分饲喂顺铂化疗的荷瘤小鼠,能更有效地抑制肿瘤生长:化疗小鼠饲喂牛初乳组分后,肿瘤直径自6 mm缩小为4.5 mm,而单独用顺铂化疗的肿瘤直径约8 mm.因此富含miR-30a的牛初乳组分能增进化疗药物的疗效.施用牛初乳组分,还可减少化疗药物的用量:单独用顺铂处理细胞18 h需20 mg/L剂量,加牛初乳组分后10 mg/L即可取得明显凋亡效果;单独用顺铂化疗荷瘤小鼠10天每次需500μg,而添加富含miR-30a的牛初乳组分后,顺铂剂量减半即可明显缩小肿瘤.

关 键 词:miR-30a  自噬  细胞凋亡  牛初乳  顺铂
收稿时间:2011-08-15
修稿时间:2012-02-28

miR-30a Enriched Colostrum-Fraction Can Inhibit The DDP-induced Autophagy of HeLa Cells and Promote The Tumor Shrink
ZOU Zhen-You,WANG Yang,DING Han-Ying,WU Lin-Ping,CHEN Shu-Mei,JIANG Ting,GUO Fang,ZHANG He-Yun,CHEN Xi,ZHANG Qi-Peng,ZENG Ke and ZHANG Chen-Yu. miR-30a Enriched Colostrum-Fraction Can Inhibit The DDP-induced Autophagy of HeLa Cells and Promote The Tumor Shrink[J]. Progress In Biochemistry and Biophysics, 2012, 39(11): 1099-1108
Authors:ZOU Zhen-You  WANG Yang  DING Han-Ying  WU Lin-Ping  CHEN Shu-Mei  JIANG Ting  GUO Fang  ZHANG He-Yun  CHEN Xi  ZHANG Qi-Peng  ZENG Ke  ZHANG Chen-Yu
Affiliation:Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China,Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China and Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences, Nanjing University, Nanjing 210093, China
Abstract:Here we firstly report that colostrum contains a high level of miR-30a. Using the miR-30a rich fraction extracted from colostrum, we successfully restrained the autophagy activity of HeLa cells induced by DDP, and promoted their apoptosis from 12.5% to 56.5% in 8 h post-treatment of DDP. By feeding the tumor-bearing mice undergoing DDP-chemotherapy with miR-30a- rich fraction from colostrum for 10 days, we reduced tumors size more effective than treating mice with DDP alone. In particular, the diameter of tumors was diminished to 4.5 mm after miR-30a-rich colostrum fraction administration during DDP chemotherapy, while the tumors treated with DDP only grown to 9.0 mm in diameter. In conclusion, the miR-30a-rich fraction of colostrum can sensitize the cancer cells to anti-cancer drugs, thus enhance the effect of chemotherapy drug on tumor treatment.
Keywords:miR-30a   autophagy   apoptosis   colostrum   cis-dichloride diamine platinum
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