The effect of oxidized low-density lipoprotein combined with adriamycin on the proliferation of Eca-109 cell line

Lipids in Health and Disease

Qing Hui Li¹  Tao Yu Diao¹  Jia Cui¹  Mei Shu Wang²  Ping Zhi Wang²  Qing D Li³  Hao Li³ 

[1] Institutes of Basic Medicine, Shandong Academy of Medical Sciences Jinan, P.R. China;College of Public Health, Shandong University, Jinan, P.R. China;Qilu Hospital, Shandong University, Jinan, P.R. China

关键词: expression;    protein;    gene;    apoptosis;    adriamycin;    low-density lipoprotein;    Esophagueal squamous cell line;   

Others  :  1212604
DOI  :  10.1186/1476-511X-10-108

 received in 2011-05-12, accepted in 2011-06-29,  发布年份 2011

【 摘 要 】

Background

The purpose of this study was to identify the affect on the proliferation Eca-109 cells treated with oxidized low-density lipoprotein (ox-LDL) combined with adriamycin (ADM).

Methods

Eca-109 cell were cultured in the presence of oxLDL/ADM, and cell proliferation tested by MTT and cell apoptosis was monitored by the proportion of apoptosis and cell cycle by flow cytomester. We simultaneously evaluated the level of associated- apoptosis Bcl-2, Bax, and Caspase-3 gene mRNA and protein.

Results

OxLDL were cytotoxic and activate apoptosis. OxLDL combined with ADM significant enhanced the proportion rate of apoptosis on a time and dose dependency. The expressions of the inhibiting apoptosis Bcl-2 gene mRNA and protein were down regulated, whereas, the expressions of the promoting apoptosis Bax, and Caspase-3 genes mRNA and protein were up regulation.

Conclusion

These results suggested that oxLDL have cytotoxicity and activate apoptosis on the Eca-109 cells. OxLDL combined with ADM have a synergistic effect on the apoptosis induced Eca-109 cells. Furthermore, oxLDL may contribute to the improvement of clinical chemotherapy of cancer need to make further investigation.

【 授权许可】

   
2011 Li et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Cohen J, Lefor AT: Nutrition support and cancer. Nutrition 2001, 17:698-699.
• [2]Silver S: EPA halts cancer-induced weight loss. Lancet Oncol 2000, 3:7.
• [3]May PE, Barber A, D'Olimpio JT: Reversal of cancer related wasting using oral supplementation with a combination of beta-hydroxy-betamethylbutyrate, arginine, and glutamine. Am J Surg 2002, 183:471-479.
• [4]Barber MD, Fearon KCH, Ross JA: Eicosapentaenoic acid modulates the immune response but has no effect on a mimic of antigen-specific responses. Nutrition 2005, 21:588-593.
• [5]Burns CP, Halabi S, Clamon GH: Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Clin Cancer Res 1999, 5:3942-3947.
• [6]Comi D, Baronzio GF, Vecchio C, Zambelli A, Cargnel A, Ferrario R, Galante F, Barlocco A, Pravettoni G: Oxygen radicals, antioxidant vitamins and minerals in AIDS cachexia. Nutrition 1997, 13:272.
• [7]Cremades O, Parrado J, Jover M, de Tera'n LC, Gutie'rrez JF, Palomas JDB: Nutritional treatment of cancer cachexia in rats --Use of a diet formulated with a crayfish enzymatic extract. Eur J Nutr 2007, 46:347-353.
• [8]Capra S, Bauer J, Davidson W, Ash S: Nutritional therapy for cancer-induced weight loss. Nutr Clin Pract 2002, 17:210-2213.
• [9]Gregg JR, Cookson MS, Phillips S, Salem S, Chang SS, Clark PE, Davis R, Stimson CJ, Aghazadeh JM, Smith JA, Barocas DA: Effect of Preoperative Nutritional Deficiency on Mortality After Radical Cystectomy for Bladder Cancer. J Urology 2011, 185:90-96.
• [10]Lu J, Mitra S, Wang X, Khaidakov M, Mehta JL: Contribution of Oxidative Stress and Lectin-like OxLDL-receptor LOX-1 in Atherogenesis and Tumorigenesis. Antioxid Redox Signal 2011.
• [11]Dotan Y, Lichtenberg D, Pinchuck I: Lipid peroxidation cannot be used as a universal criterion of oxidative stress. Prog Lipid Res 2004, 43:200-227.
• [12]Saintot M, Astre C, Pujol H, Gerber M: Tumor progression and oxidant-antioxidant status. Carcinogenesis 1996, 17(6):1267-1271.
• [13]Guyton KZ, Kensler TW: Oxidative mechanisms in carcinogenesis. Br Med Bull 1993, 49:523-544.
• [14]Ray G, Husain SA: Role of lipids, lipoproteins and vitamins in women with breast cancer. Clin Biochem 2001, 34:71-76.
• [15]Ray G, Batra S, Shukla NK, Deo S, Raina V, Ashor S, Husain SA: Lipid peroxidation, free radical, and antioxidant status in breast cancer. Breast Cancer Res Treat 2000, 59:163-170.
• [16]Uchida K: 4-hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog Lipid Res 2003, 42:318-343.
• [17]Chung FL, Nath RG, Ocando J, Nishikawa A, Zhang L: Deoxyguanosine adducts of t-4-hydroxy-2-nonenal are endogenous DNA lesions in rodents and humans: detection and potential sources. Cancer Res 2000, 60:1507-1511.
• [18]Sonoda I, Imoto I, Inoue J, Shibata T, Shimada Y, Chin K, Imamura M, Amagasa T, Gray JW, Hirohashi S, Inazawa J: Frequent silencing of low density lipoprotein receptor-related protein 1B (LRP1B) expression by genetic and epigenetic mechanisms in esophageal squamous cell carcinoma. Cancer Res 2004, 64:3741-3747.
• [19]Yang YF, Li H, Xu XQ, Diao YT, Fang XF, Wang Y, Zhao DL, Wu K, Li HQ: An expression of squamous cell carcinoma antigen 2 in peripheral blood within the different stages of esophageal carcinogenesis. Dis Esophagus 2008, 21:395-401.
• [20]Wang Yan, Li Hao, Diao Yutao, Li Hui-qing, Zhang Yukun, Yin Chang, Cui Yongchun, Ma Qing, Fang Xueqiang, Zhou Yingzhi, Yang Yanfang: Relationship between oxidized LDL antibodies and different stages of esophageal carcinogenic progressionAcknowledgements. Archives of Medical Research 2008, 39:760-767.
• [21]Diao YT, Li H, Li HQ, Zhou YZ, Ma Q, Wang Y, Li D: Association of serum levels of lipid and its novel constituents with the different stages of esophageal carcinoma. Lipids in Health and Disease 2009, 8:48-50. BioMed Central Full Text
• [22]Hida T, Ueda R, Takahashi T, Watanabe H, Kato T, Suyama M, Sugiura T, Ariyoshi Y, Takahashi T: Chemosensitivity and radiosensitivity of small cell lung cancer cell lines studied by a newly developed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) hybrid assay. Cancer Res 1989, 49:4785-4790.
• [23]Manoharan S, Kolanjiappan K, Kayalvizhi M: Enhanced lipidperoxidation and impaired enzymic antioxidant activities in theerythrocytes of patients with cervical carcinoma. Cell Mol Biol Lett 2004, 9:699-707.
• [24]Warnick GR, Knopp RH, Fitzpatrick V, Branson L: Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints. Clin Chem 1990, 36:15-9.
• [25]Argile's JM, A ' lvarez B, Lo'pez-Soriano FJ: The metabolic basis of cancer cachexia. Med Res Rev 1997, 175:477-498.
• [26]Fried SK, Zechner R: Cachectin/tumor necrosis factor decreases human adipose tissue lipoprotein lipase mRNA levels, synthesis, and activity. J Lipid Res 1989, 30:1917-1923.
• [27]Delimaris I, Faviou E, Antonakos G, Stathopoulou E, Zachari A, Dionyssiou-Asteriou A: Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer. Clin Biochem 2007, 40:1129-1134.
• [28]Suzuki K, Ito Y, Wakai K, Kawado M, Hashimoto S, Toyoshima H, Kojima M, Tokudome S, Hayakawa N, Watanabe Y, Tamakoshi K, Suzuki S, Ozasa K, Tamakoshi A, Japan Collaborative Cohort Study Group: Serum oxidized low-density lipoprotein levels and risk of colorectal cancer: A case-control study nested in the Japan collaborative cohort study. Cancer Epidemiol Biomarkers Prev 2004, 13:1781-1787.
• [29]Mueller E, Smith M, Sarraf P, Kroll T, Aiyer A, Kaufman DS, Oh W, Demetri G, Figg WD, Zhou XP, Eng C, Spiegelman BM, Kantoff PW: Effects of ligand activation of peroxisome proliferator- activated receptor gamma in human prostate cancer. Proc.Natl Acad Sci USA 2000, 97:10990-10995.
• [30]Stepsenwol J: Carcinogenic effect of cholesterol in mice. Proc Soc Exp Biol Med 1966, 121:168-171.
• [31]Guyton KZ, Kensler TW: Oxidative mechanisms in carcinogenesis. Br Med Bull 1993, 49:481-483.
• [32]Uchida K: 4-hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog Lipid Res 2003, 42:318-343.
• [33]Sanchez-Perez Y, Carrasco-Legleu C, Garcia-Cuellar C, Perez-Carreon J, Hernandez-Garcia S, Salcido-Neyoy M, Alemán-Lazarini L, Villa-Treviño S: Oxidative stress in carcinogenesis. Correlation between lipid peroxidation and induction of preneoplastic lesions in rat hepatocarcinogenesis. Cancer Lett 2005, 217:25-32.
• [34]Wiseman H, Halliwell B: Damage to DNA by reactive oxygen and nitrogen species; role in inflammatory disease and progression to cancer. Biochem J 1996, 313:17-19.
• [35]Zettler ME, Prociuk MA, Austria JA, Massaeli H, Zhong G, Pierce GN: oxLDL stimulates cell proliferation through a general induction of cell cycle proteins. J Am Physiol Heart Circ Physiol 2003, 284:H644-53.
• [36]Han CY, Pak YK: Oxidation-dependent effects of oxidized LDL proliferation or cell death. Exp Mol Med 1999, 31:165-73.
• [37]Motta M, Pistone G, Franzone AM, Romeo MA, Di Mauro S, Giugno L, Ruello P, Malaguarnera M: Antibodies against ox-LDL serum levels in patients with hepatocellular carcinoma. Panminerva Med 2003, 45:69-73.
• [38]Kontush A, Spranger T, Reich A, Djahansouzi S, Karten B, Braesen JH, Finckh B, Kohlschütter A, Beisiegel U: Whole plasma oxidation assay as a measure of lipoprotein oxidizability. BioFactors 1997, 6:99-109.
• [39]Scoles DR, Xu X, Wang H, Tran H, Taylor-Harding B, Li A, Karlan BY: Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein. Gynecol Oncol 2010, 116:109-116.
• [40]Zabirnyk O, Liu W, Khalil S, Sharma A, Phang JM: Oxidized low-density lipoproteins upregulate praline oxidase to initiate ROS-dependent autophagy. Carcinogenesis 2010, 31:446-454.
• [41]Ginter E: Blood cholesterol levels and mortality in cancer. Bratisl Lek Listy 1990, 91:70-76.
• [42]Tamakoshi A, Ohno Y, Suzuki S, Kawamura T, Wakai K, Nakamura R: Epidemiological remarks on low serum cholesterol level and cancer risk of all sites. Nippon Koshu Eisei Zasshi 1994, 41:393-403.
• [43]Karvonen J, Päivänsalo M, Kesäniemi YA, Hörkkö S: Circulation Immunoglobulin M type of autoantibodies to oxidized low-density lipoprotein has an inverse relation to carotid artery atherosclerosis. Circulation 2003, 108:2107-2112.
• [44]Delimaris I, Faviou E, Antonakos G, Stathopoulou E, Zachari A, Dionyssiou-Asteriou A: Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer. Clin Biochem 2007, 40:1129-1134.
• [45]Parsons SK, Skapek SX, Neufeld EJ, Kuhlman C, Young ML, Donnelly M, Brunzell JD, Otvos JD, Sallan SE, Rifai N: Asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia. Blood 1997, 89(6):1886-1895.
• [46]Wakatsuki A, Ogawa Y, Saibara T, Okatani Y, Fukaya T: Size and oxidative susceptibility of low-density lipoprotein particles in breast cancer patients with tamoxifen-induced fatty liver. J Clin Endocrinol Metab 2002, 87:3676-3681.
• [47]Capra Sandra, Bauer Judith, Davidson Wendy, Susan Ash: Nutritional Therapy for Cancer-Induced Weight Loss. Nutrition in Clinical Practice 2002, 17:210-213.