CpG ODN对卡铂治疗Lewis肺癌小鼠移植瘤的增敏效应

doi:10.3969/j.issn.1004-616x.2010.02.004

癌变·畸变·突变 ›› 2010, Vol. 22 ›› Issue (2): 95-099.doi: 10.3969/j.issn.1004-616x.2010.02.004

CpG ODN对卡铂治疗Lewis肺癌小鼠移植瘤的增敏效应

乔田奎;袁素娟;陈伟;庄喜兵

复旦大学附属金山医院放疗科，上海 200540

收稿日期:2009-06-29 修回日期:2009-11-26 出版日期:2010-03-30 发布日期:2010-03-30
通讯作者: 乔田奎

Enhancing effect of CpG ODN on sensitivity of Lewis lung cancer to carboplatin in mice

QIAO Tian-kui;YUAN Su-juan;CHEN Wei;ZHUANG Xi-bing

Department of Radiation Therapy, Jinshan Hospital, Fudan University, Shanghai 200540, China

Received:2009-06-29 Revised:2009-11-26 Online:2010-03-30 Published:2010-03-30
Contact: QIAO Tian-kui

摘要/Abstract

摘要： 目的：探讨含胞嘧啶-磷酸盐-鸟嘌呤基序的寡脱氧核苷酸(cytosine-phosphate-guanine oligodeoxynucleotide, CpG ODN)对卡铂治疗Lewis肺癌荷瘤小鼠的化疗增敏作用。方法：在小鼠右前肢腋窝接种Lewis肺癌细胞，制备荷瘤小鼠模型，将32只荷瘤小鼠随机分为4组：对照组，不做任何处理；卡铂治疗组，第1～5天每天腹腔注射卡铂注射液0.32 mg；CpG组，第1～5天每次腹腔注射CpG ODN(1826)0.05 mg；CpG＋卡铂组，每次卡铂注射前6 h腹腔注射CpG ODN(1826)。观察各组移植瘤生长速度和重量，HE染色法观察移植瘤组织病理变化，TUNEL法检测细胞凋亡。结果：成功建立Lewis肺癌荷瘤小鼠模型。各治疗组小鼠肿瘤体积都较对照组明显减小(P<0.01)，其中CpG＋卡铂组移植瘤体积最小；卡铂组、CpG组、CpG＋卡铂组的抑瘤率分别为23.35％、21.47％、48.43％；HE染色法观察到各治疗组移植瘤的坏死均较对照组明显，其中CpG＋卡铂组最明显。TUNEL法检测对照组瘤组织细胞凋亡率为2.75％±0.89％，卡铂组为4.87％±1.13％，CpG组为7.63％±1.41％，CpG＋卡铂组为32.63％±4.66％，各治疗组瘤细胞凋亡率均明显高于对照组(P均<0.01)，其中CpG＋卡铂组显著高于单独卡铂组和单独CpG组(P均<0.01)。结论： CpG ODN(1826)能明显提高Lewis肺癌移植瘤对卡铂治疗的化疗敏感性，促进肿瘤细胞凋亡。

关键词: 胞嘧啶-磷酸盐-鸟嘌呤基序寡脱氧核苷酸, Lewis肺癌, 化疗敏感性, 卡铂, 细胞凋亡

Abstract: OBJECTIVE: To explore the role of cytosine-phosphate oligodeoxynucleotides (CpG ODN) in enhancing the sensitivity to carboplatin in mouse with Lewis lung cancer. METHODS: The tumor-bearing mouse model was induced by injecting Lewis lung cancer cells into the right infra-axillary dermis. 32 C57BL mice were evenly randomized into 4 groups. Group A: control group; Group B: carboplatin group; Group C: CpG group; Group D: CpG plus carboplatin group. Group B was treated with carboplatin only(0.32mg/d, on day1,2,3,4,5). Group C received CpG ODN 0.05 mg on day 1,2,3,4,5. Group D was treated with CpG ODN 6 h before carboplatin. Tumor growth and tumor weight were observed in all groups. The pathological change of the tumor was evaluated with HE staining and apoptosis of tumor cells were examined with TUNEL method. RESULTS: The Lewis lung cancer-bearing model was successfully established in mice. The tumor volumes of treatment groups were smaller than that in control group (P<0.01)，and the tumor volumes of group D was the smallest. The rates of tumor were 23.35％ in group B, 21.47％ in group C, and 48.43％ in group D. HE staining showed that tumor necrosis in group B, C, and D was more severe than that of control group, with the most severe one in group D. The apoptosis rates were (2.75±0.89)％ in group A，(8.88±1.13)％ in group B, (7.63±1.41)％ in group C, and (31.13±4.67)％ in group D. The apoptosis rate of every treated group was higher than that in the control group, with group D significantly higher than those of group B and C(P<0.01). CONCLUSION: CpG ODN could dramatically increase the chemo-sensitivity of tumor cells and promote their apoptosis.

Key words: cytosine-phosphate-guanine oligodeoxynucleotides, Lewis lung cancer, chemo-sensitivity, carboplatin, apoptosis

中图分类号:

R734.2

乔田奎, 袁素娟, 陈伟, 庄喜兵. CpG ODN对卡铂治疗Lewis肺癌小鼠移植瘤的增敏效应[J]. 癌变·畸变·突变, 2010, 22(2): 95-099.

QIAO Tian-kui, YUAN Su-juan, CHEN Wei, ZHUANG Xi-bing. Enhancing effect of CpG ODN on sensitivity of Lewis lung cancer to carboplatin in mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2010, 22(2): 95-099.

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CpG ODN对卡铂治疗Lewis肺癌小鼠移植瘤的增敏效应

Enhancing effect of CpG ODN on sensitivity of Lewis lung cancer to carboplatin in mice

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