
浏览全部资源
扫码关注微信
纸质出版:2017-04
移动端阅览
常杏, 胡长江, 邓盛瑜, 等. 端粒酶逆转录酶线粒体转位促进肝癌细胞干性及耐药的研究[J]. 第三军医大学学报, 2017,39(8):781-786.
Xin Chang, Changjiang Hu, Shengyu Deng, et al. Mitochondrial translocation of human telomerase reverse enzyme promotes stemness and drug-resistance of hepatocellular carcinoma cells[J]. Journal of Third Military Medical University, 2017, 39(8): 781-786.
常杏, 胡长江, 邓盛瑜, 等. 端粒酶逆转录酶线粒体转位促进肝癌细胞干性及耐药的研究[J]. 第三军医大学学报, 2017,39(8):781-786. DOI: 10.16016/j.1000-5404.201610159.
Xin Chang, Changjiang Hu, Shengyu Deng, et al. Mitochondrial translocation of human telomerase reverse enzyme promotes stemness and drug-resistance of hepatocellular carcinoma cells[J]. Journal of Third Military Medical University, 2017, 39(8): 781-786. DOI: 10.16016/j.1000-5404.201610159.
Objective
2
To determine the effect of mitochondrial translocation of human telomerase reverse enzyme (hTERT) on the stemness and drug-resistance of hepatocellular carcinoma (HCC) cells.
Methods
2
Human HCC cell lines HepG2 and Huh7 were exposed intermittently to cisplatin (CDDP) to obtain cisplatin-resistant cell lines HepG2/CDDP and Huh7/CDDP. CCK-8 assay was employed to detect cell sensitivity to CDDP. Western blotting was adopted to detect hTERT protein level in the mitochondria
and mitochondrial membrane potential was measured by confocal laser scanning microscopy. Flow cytometry was used to detect the expression of cell stemness-related proteins CD133 and EpCAM
and the colony formation ability of the cells was assessed with colony formation assay; Western blotting was used to detect the expression level of stemness-related factor OCT-4.
Results
2
The resistance indexes of CDDP-resistant HepG2 and Huh7 cells were significantly increased compared with their parental cells (HepG2: 41.16±0.42
vs
7.69±0.86 μg/mL; Huh7: 33.48±0.33
vs
7.18±0.35 μg/mL
P
<
0.01). The CDDP-resistant cells exhibited significantly increased mitochondrial hTERT expression and mitochondrial membrane potential with increased proportions of CD133
+
cells (HepG2: 1.44±0.41
HepG2/CDDP: 23.15±1.55
P
<
0.01) and EpCAM
+
cells (HepG2: 0.85±0.10
HepG2/CDDP: 3.96±0.10
P
<
0.01). The resistant cells also showed significantly enhanced colony formation ability and increased expression of OCT-4 protein.
Conclusion
2
The translocation of mitochondrial hTERT is significantly increased in CDDP-resistant cells
which possess obvious phenotypes of tumor stem cells.
Miyajima A Tanaka M Itoh T Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogram-ming Cell Stem Cell 2014 14 5 561 574 10.1016/j.stem.2014.04.010 Miyajima A, Tanaka M, Itoh T. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogram-ming [J]. Cell Stem Cell, 2014, 14(5): 561-574. DOI:10. 1016/j.stem.2014.04.010.
Siddik Z H Cisplatin: mode of cytotoxic action and molecular basis of resistance Oncogene 2003 22 47 7265 7279 10.1038/sj.onc.1206933 Siddik Z H. Cisplatin: mode of cytotoxic action and molecular basis of resistance[J]. Oncogene, 2003, 22(47): 7265-7279. DOI:10.1038/sj.onc.1206933.
Liu F S Mechanisms of chemotherapeutic drug resistance in cancer therapy--a quick review Taiwan J Obstet Gynecol 2009 48 3 239 244 10.1016/S1028-4559(09)60296-5 Liu F S. Mechanisms of chemotherapeutic drug resistance in cancer therapy--a quick review[J]. Taiwan J Obstet Gynecol, 2009, 48(3): 239-244. DOI:10.1016/S1028-4559(09)60296-5.
Kuo K K Lee K T Chen K K Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer Stem Cells 2016 34 11 2613 2624 10.1002/stem.2447 Kuo K K, Lee K T, Chen K K, et al. Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer[J]. Stem Cells, 2016, 34(11): 2613-2624. DOI:10. 1002/stem.2447.
Bram E E Stark M Raz S Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance Neoplasia 2009 11 12 1359 1370 10.1593/neo.91314 Bram E E, Stark M, Raz S, et al. Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance[J]. Neoplasia, 2009, 11(12): 1359-1370. DOI:10.1593/neo.91314.
McIntosh K Balch C Tiwari A K Tackling multidrug resistance mediated by efflux transporters in tumor-initiating cells Expert Opin Drug Metab Toxicol 2016 12 6 633 644 10.1080/17425255.2016.1179280 McIntosh K, Balch C, Tiwari A K. Tackling multidrug resistance mediated by efflux transporters in tumor-initiating cells[J]. Expert Opin Drug Metab Toxicol, 2016, 12(6): 633-644. DOI:10.1080/17425255.2016.1179280.
Deville L Hillion J Pendino F hTERT promotes imatinib resistance in chronic myeloid leukemia cells: therapeutic implications Mol Cancer Ther 2011 10 5 711 719 10.1158/1535-7163.MCT-10-0979 Deville L, Hillion J, Pendino F, et al. hTERT promotes imatinib resistance in chronic myeloid leukemia cells: therapeutic implications[J]. Mol Cancer Ther, 2011, 10(5): 711-719. DOI:10.1158/1535-7163.MCT-10-0979.
Liu N Ding D Hao W hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor Nucleic Acids Res 2016 44 18 8693 8703 10.1093/nar/gkw549 Liu N, Ding D, Hao W, et al. hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor[J]. Nucleic Acids Res, 2016, 44(18): 8693-8703. DOI:10.1093/nar/gkw549.
Jafri M A Ansari S A Alqahtani M H Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies Genome Med 2016 8 1 69 10.1186/s13073-016-0324-x Jafri M A, Ansari S A, Alqahtani M H, et al. Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies[J]. Genome Med, 2016, 8(1): 69. DOI:10.1186/s13073-016-0324-x.
张 丹 郝 宁波 唐 波 miR-1182调控胃癌细胞人端粒酶反转录酶的分子机制及其对迁移能力的影响 第三军医大学学报 2014 36 10 1074 1077 10.16016/j.1000-5404.2014.10.033 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201401234 张丹, 郝宁波, 唐波, 等. miR-1182调控胃癌细胞人端粒酶反转录酶的分子机制及其对迁移能力的影响[J].第三军医大学学报, 2014, 36(10):1074-1077. DOI:10.16016/j.1000-5404.2014.10.033.
Zhang Dan Hao Ningbo Tang Bo Mechanism of miR-1182 regulating human telomerase reverse transcriptase in gastric cancer cells and its effect on cell migration capability J Third Mil Med Univ 2014 36 10 1074 1077 10.16016/j.1000-5404.2014.10.033 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201401234 Zhang Dan, Hao Ningbo, Tang Bo, et al. Mechanism of miR-1182 regulating human telomerase reverse transcriptase in gastric cancer cells and its effect on cell migration capability[J]. J Third Mil Med Univ, 2014, 36(10):1074-1077. DOI:10.16016/j.1000-5404.2014.10.033.
Saretzki G Extra-telomeric functions of human telomerase: cancer, mitochondria and oxidative stress Curr Pharm Des 2014 20 41 6386 6403 10.2174/1381612820666140630095606 Saretzki G. Extra-telomeric functions of human telomerase: cancer, mitochondria and oxidative stress[J]. Curr Pharm Des, 2014, 20(41): 6386-6403. DOI:10.2174/1381612820666140630095606.
Santos J H Meyer J N Skorvaga M Mitochondrial hTERT exacerbates free-radical-mediated mtDNA damage Aging Cell 2004 3 6 399 411 10.1111/j.1474-9728.2004.00124.x Santos J H, Meyer J N, Skorvaga M, et al. Mitochondrial hTERT exacerbates free-radical-mediated mtDNA damage[J]. Aging Cell, 2004, 3(6): 399-411. DOI:10.1111/j.1474-9728.2004.00124.x.
Sharma N K Reyes A Green P Human telomerase acts as a hTR-independent reverse transcriptase in mitochondria Nucleic Acids Res 2012 40 2 712 725 10.1093/nar/gkr758 Sharma N K, Reyes A, Green P, et al. Human telomerase acts as a hTR-independent reverse transcriptase in mitochondria[J]. Nucleic Acids Res, 2012, 40(2): 712-725. DOI:10. 1093/nar/gkr758.
Haendeler J Drose S Buchner N Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage Arterioscler Thromb Vasc Biol 2009 29 6 929 935 10.1161/atvbaha.109.185546 Haendeler J, Drose S, Buchner N, et al. Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage[J]. Arterioscler Thromb Vasc Biol, 2009, 29(6): 929-935. DOI:10.1161/atvbaha.109.185546.
Indran I R Hande M P Pervaiz S hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells Cancer Res 2010 71 1 266 276 10.1158/0008-5472.can-10-1588 Indran I R, Hande M P, Pervaiz S. hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells[J]. Cancer Res, 2010, 71(1): 266-276. DOI:10. 1158/0008-5472.can-10-1588.
Singhapol C Pal D Czapiewski R Mitochondrial telomerase protects cancer cells from nuclear DNA damage and apoptosis PLoS ONE 2013 8 1 e52989 10.1371/journal.pone.0052989 Singhapol C, Pal D, Czapiewski R, et al. Mitochondrial telomerase protects cancer cells from nuclear DNA damage and apoptosis[J]. PLoS ONE, 2013, 8(1): e52989. DOI:10.1371/journal.pone.0052989.
Ling X Zhou Y Li S W Modulation of mitochondrial permeability transition pore affects multidrug resistance in human hepatocellular carcinoma cells Int J Biol Sci 2010 6 7 773 783 10.7150/ijbs.6.773 Ling X, Zhou Y, Li S W, et al. Modulation of mitochondrial permeability transition pore affects multidrug resistance in human hepatocellular carcinoma cells[J]. Int J Biol Sci, 2010, 6(7): 773-783. DOI:10.7150/ijbs.6.773.
Ling X Wen L Zhou Y Role of mitochondrial translocation of telomerase in hepatocellular carcinoma cells with multidrug resistance Int J Med Sci 2012 9 7 545 554 10.7150/ijms.4648 Ling X, Wen L, Zhou Y. Role of mitochondrial translocation of telomerase in hepatocellular carcinoma cells with multidrug resistance[J]. Int J Med Sci, 2012, 9(7): 545-554. DOI:10.7150/ijms.4648.
Yan J Zhou Y Chen D Effects of mitochondrial translocation of telomerase on drug resistance in hepatocellular carcinoma cells J Cancer 2015 6 2 151 159 10.7150/jca.10419 Yan J, Zhou Y, Chen D, et al. Effects of mitochondrial translocation of telomerase on drug resistance in hepatocellular carcinoma cells[J]. J Cancer, 2015, 6(2): 151-159. DOI:10.7150/jca.10419.
Santos J H Meyer J N Van Houten B Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis Hum Mol Genet 2006 15 11 1757 1768 10.1093/hmg/ddl098 Santos J H, Meyer J N, Van Houten B. Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis[J]. Hum Mol Genet, 2006, 15(11): 1757-1768. DOI:10.1093/hmg/ddl098.
Haendeler J Drose S Buchner N Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage Arterioscler Thromb Vasc Biol 2009 29 6 929 935 10.1161/atvbaha.109.185546 Haendeler J, Drose S, Buchner N, et al. Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage[J]. Arterioscler Thromb Vasc Biol, 2009, 29(6): 929-935. DOI:10.1161/atvbaha.109.185546.
Indran I R Hande M P Pervaiz S hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells Cancer Res 2011 71 1 266 276 10.1158/0008-5472.can-10-1588 Indran I R, Hande M P, Pervaiz S. hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells[J]. Cancer Res, 2011, 71(1): 266-276. DOI:10.1158/0008-5472.can-10-1588.
Kovalenko OA Kaplunov J Herbig U Expression of (NES-) hTERT in cancer cells delays cell cycle progression and increases sensitivity to genotoxic stress PLoS ONE 2010 5 5 e10812 10.1371/journal.pone.0010812 Kovalenko OA, Kaplunov J, Herbig U, et al. Expression of (NES-) hTERT in cancer cells delays cell cycle progression and increases sensitivity to genotoxic stress[J]. PLoS ONE, 2010, 5(5): e10812. DOI:10.1371/journal.pone.0010812.
Kovalenko O A Caron M J Ulema P A mutant telomerase defective in nuclear-cytoplasmic shuttling fails to immortalize cells and is associated with mitochondrial dysfunction Aging Cell 2010 9 2 203 219 10.1111/j.1474-9726.2010.00551.x Kovalenko O A, Caron M J, Ulema P, et al. A mutant telomerase defective in nuclear-cytoplasmic shuttling fails to immortalize cells and is associated with mitochondrial dysfunction[J]. Aging Cell, 2010, 9(2): 203-219. DOI:10.1111/j.1474-9726.2010.00551.x.
Balaban R S Nemoto S Finkel T Mitochondria, oxidants, and aging Cell 2005 120 4 483 495 10.1016/j.cell.2005.02.001 Balaban R S, Nemoto S, Finkel T. Mitochondria, oxidants, and aging[J]. Cell, 2005, 120(4): 483-495. DOI:10.1016/j.cell.2005.02.001.
Zhou D Shao L Spitz D R Reactive oxygen species in normal and tumor stem cells Adv Cancer Res 2014 122 1 67 10.1016/B978-0-12-420117-0.00001-3 Zhou D, Shao L, Spitz D R. Reactive oxygen species in normal and tumor stem cells[J]. Adv Cancer Res, 2014, 122: 1-67. DOI:10.1016/B978-0-12-420117-0.00001-3.
Madungwe N B Zilberstein N F Feng Y Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart Am J Cardiovasc Dis 2016 6 3 93 108 https://www.researchgate.net/publication/308762709_Critical_role_of_mitochondrial_ROS_is_dependent_on_their_site_of_production_on_the_electron_transport_chain_in_ischemic_heart Madungwe N B, Zilberstein N F, Feng Y, et al. Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart[J]. Am J Cardiovasc Dis, 2016, 6(3): 93-108.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621