为探讨线粒体腺苷酸转运体（ANT）在宫颈癌组织中的表达变化及其与细胞凋亡的关系，收集维吾尔族妇女浸润性宫颈鳞癌患者的组织36 例，正常或者慢性宫颈炎宫颈组织32 例作为对照。分别运用荧光定量PCR（Q-PCR）、蛋白免疫印迹（westernblot，WB）技术，检测线粒体腺苷酸转运体ANT1、ANT2、ANT3，以及Bax、Bcl-2、p53 在不同宫颈组织中的mRNA 和蛋白表达水平及其差异。运用TUNEL 法测定不同宫颈组织中的细胞凋亡程度。Q-PCR 和WB 结果显示，与正常对照组相比，p53、Bax 在宫颈癌患者宫颈组织中表达降低，而Bcl-2 和ANT3 表达升高，差异有统计学意义（P<0.05）。TUNEL 结果显示，宫颈癌组的凋亡指数（AI）明显高于正常对照宫颈炎组，两组之间差异有统计学意义（P<0.05）。线粒体腺苷酸转运体ANT 在宫颈癌组织中的异常表达导致线粒体功能紊乱，从而干扰细胞凋亡过程，这可能是宫颈癌发生与发展的一个重要机制。
To investigate the association of the cell apoptosis with the expression change of adenine nucleotide translocator (ANT) in the tissue of Uighur women with cervical cancer, we collected cervical tissue samples from Uygur women with cervical lesions (invasive cervical cancer (ICC): 36 cases and cervicitis: 32 cases). The mRNA and protein expression levels of ANT1, ANT2, ANT3, Bax, Bcl-2, and P53 in the tissues from the two groups were examined by real-time fluorescence quantitative PCR (Q-PCR) and western blot (WB). Apoptotic activity of cervical epithelium cells from the two groups was studied by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) method. The results of Q-PCR and WB show that compared with the cervicitis group, the expressions of p53 and Bax in the ICC group decreased while the expressions of Bcl-2 and ANT3 increased, and the difference was statistically significant (P<0.05). The TUNEL results showed that the apoptosis index (AI) of the ICC group was obviously higher than that of the normal control cervicitis groups, the difference between the two groups was statistically significant (P<0.05). The abnormal expression of ANT in cervical cancer leads to mitochondrial dysfunction, thus interfering the apoptosis process, which may be an important mechanism of the occurrence and development of cervical cancer.
[1] 刘开江, 刘继文, 李晓荣, 等. 新疆维、汉妇女宫颈癌发病危险因素的 流行病学研究[J]. 新疆医科大学学报, 2008, 31(10): 1335-1338. Liu Kaijiang, Liu Jiwen, Li Xiaorong, et al. Epidemiology study of risk factors on Uigur and Han cervical cancer in Xinjiang[J]. Journal of Xinjiang Medical University, 2008, 31(10): 1335-1338.
[2] 拉莱·苏祖克, 彭玉华, 周康, 等. 新疆不同民族宫颈癌发病趋势分析[J]. 新疆医科大学学报, 2006, 29(7): 569-571. Suzuke Lalai, Peng Yuhua, Zhou Kang, et al. The analysis of cervical cancer morbidity of various ethnic groups in Xinjiang[J]. Journal of Xinjiang Medical University, 2006, 29 (7): 569-571.
[3] 张国庆, 刘开江, 赖小军, 等. 新医大附属肿瘤医院1989—2002年住 院病人恶性肿瘤分布[J]. 新疆医科大学学报, 2003, 26(4): 393-395. Zhang Guoqing, Liu Kaijiang, Lai Xiaojun, et al. Distribution of malignant tumor patients in hospital from 1989 to 2002 in the Affiliated Tumor Hospital of Xinjiang Medical University[J]. Journal of Xinjiang Medical University, 2003, 26(4): 393-395.
[4] Jourdain A, Martinou J C. Mitochondrial outer-membrane permeabilization and remodelling in apoptosis[J]. International Journal of Biochemistry & Cell Biology, 2009, 41(10): 1884-1889.
[5] Duarte F V, Gomes A P, Teodoro J S, et al. Dibenzofuran-induced mitochondrial dysfunction: Interaction with ANT carrier[J]. Toxicology in Vitro, 2013, 27(8): 2160-2168.
[6] Cirri P, Chiarugi P. Tumors and their stroma: Mitochondria at the crossroad[J]. Cell Cycle, 2013, 12(2): 204-205.
[7] Lipponen P, Aaltomaa S. Apoptosis in bladder cancer as related to standard prognostic factors and prognosis[J]. Journal of Pathology, 1994, 173(4): 333-339.
[8] Lipponen P, Aaltomaa S, Kosma V A. Apoptosis in breast cancer as related histopathological characteristics and prognosis[J]. European Journal of Cancer, 1994, 30A(14): 2068-2073.
[9] Brambilla E, Negoescu A, Gazzeri S, et al. Apoptosis related factors p53, Bcl-2, and Bax in neuroendocrine lung tumors[J]. American Journal of Pathology, 1996, 149(6): 1941-1952.
[10] Vyssokikh M Y, Brdiczka D. The function of complexes between the outer mitochondrial membrane pore (VDAC) and the adenine nucleotide translocase in regulation of energy metabolism and apoptosis[J]. Acta biochimica Polonica, 2003, 50(2): 389-404.
[11] Liu Y, Chen X J. Adenine nucleotide translocase, mitochondrial stress, and degenerative cell death[J]. Oxid Med Cell Longevity, 2013, 2013: ID146860.
[12] Halestrap A P, Brenner C. The adenine nucleotide translocase: Acentral component of the mitochondrial permeability transition pore and key player in cell death[J]. Current Medicinal Chemistry, 2003, 10(16): 1507-1525.
[13] Gallerne C, Touat Z, Chen Z X, et al. The fourth isoform of the adenine nucleotide translocator inhibits mitochondrial apoptosis in cancer cells[J]. International Journal of Biochemistry & Cell Biology, 2010, 42(5): 623-629.
[14] Belzacq A S, Brenner C. The adenine nucleotide translocator: A new potential chemotherapeutic target[J]. Current Drug Targets, 2003, 4 (7): 517-524.
[15] Sharaf el dein O, Mayola E, Chopineau J, et al. The adenine nucleotide translocase 2, a mitochondrial target for anticancer biotherapy[J]. Current Drug Targets, 2011, 12(6): 894-901.
[16] Belzacq A S, Vieira H L, Verrier F. Bcl-2 and Bax modulate adeninenucleotide translocase activity[J]. Cancer Reseach, 2003, 63: 541-546.
[17] Chiu T L, Su C C. Curcumin inhibits proliferation and migration by increasing the Bax to Bcl-2 ratio and decreasing NF-kappaBp65 expression in breast cancer MDA-MB-231 cells[J]. International Journal of Molecular Medicine, 2009, 23(4): 469-475.
