Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of dietary changes from high-fat diet to normal diet on breast cancer growth and metastasis

고지방식이에서 일반식이로의 전환이 유방암의 성장 및 전이에 미치는 영향

  • Received : 2020.05.18
  • Accepted : 2020.06.18
  • Published : 2020.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: It has been previously reported that breast tumor incidence, growth, and metastasis are stimulated by high-fat diet but reduced by caloric restriction. However, few studies have elucidated the effects of dietary change from a high-fat diet after breast cancer initiation. Therefore, in this study, we attempted to provide practical assistance to breast cancer prevention and management by investigating the effects of dietary change from a high-fat diet to normal diet on breast cancer growth and metastasis. Methods: The experimental animals were divided into 2 groups (high-fat diet control [HFC] group and diet restriction [DR] group) and consumed a high-fat diet for 8 weeks. 4T1 cells were transplanted into subcutaneous fat or tail vein to measure the growth and metastasis of breast cancer. The HFC and DR groups continuously ingested either high-fat diet or AIG-93G diet for 5 weeks or 3 weeks, respectively. Cell proliferation and apoptosis markers from tumor tissues were analyzed by Western blot analysis. The data were analyzed using the SPSS 25.0 package program. Results: The results show that the DR group significantly reduced breast tumor initiation, growth, and tumor tissue weight compared to the HFC group. The DR group suppressed tumor growth by decreasing proliferation and inducing apoptosis through down-regulation of Bcl-xL and up-regulation of caspase-3 activity. Furthermore, the DR group significantly reduced numbers of metastasized tumors in lung tissues. Conclusion: These results suggest that dietary change from a high-fat diet to normal diet decreased breast growth by reducing cell proliferation and inducing apoptosis and metastasis. Taken together, these results indicate that dietary change to a low-fat and balanced diet might suppress breast tumor growth and metastasis even after tumor diagnosis.

본 연구에서는 일반식이로의 식이 제한이 고지방식이로 촉진된 유방암의 성장과 전이에 미치는 영향과 그 기전을 알아보았다. 8주간 고지방식이를 섭취시킨 후 유방암을 유방 조직에 이식하거나 꼬리 정맥으로 통해 전이시켰으며, 암 생성 및 전이 후 HFC군은 고지방식이를, DR군은 일반식이로 전환시켜 사육하였다. 본 연구 결과, 원발성 유방암의 경우, HFC군과 DR군의 체중에는 차이가 없었으나 간과 비장, 신장 주변의 지방세포의 무게에서 유의한 차이를 보였다. DR군이 HFC군에 비해 유방암의 개시를 지연시켰으며, 유방암의 성장과 무게를 유의하게 감소시켰다. 일반식이로의 전환에 의한 유방암 성장 억제는 세포 분열 억제와 세포사멸을 조절하는 인자의 발현 감소에 의한 caspase-3의 활성 촉진에 의한 것으로 나타났다. 또한, 식이 제한은 폐로 전이된 유방암의 수를 유의미하게 감소시켰다. 본 실험 결과, 일반식이로의 제한은 고지방식이로 촉진된 유방암의 성장과 전이를 억제하는 효과를 나타내며, 이는 유방암 세포의 성장 억제와 사멸 유도에 의한 것으로 나타났다. 따라서, 유방암의 성장이나전이를 억제하기 위해서는 총 섭취 열량을 조절하고, 지방의 섭취량을 줄이는 균형 잡힌 식이를 섭취하도록 해야 할 것으로 사료된다.

Keywords

References

  1. Statistics Korea. Korean Statistical Information Service Resource Page [Internet]. Daejeon: Statistics Korea; 2020 [cited 2020 Jan 29]. Available from: http://kosis.kr/statisticsList/statisticsListIndex.do?menuId=M_01_01 &vwcd=MT_ZTITLE &parmTabId=M_01_01.
  2. National Cancer Center. National Cancer Information Center Resource Page [Internet]. Goyang: National Cancer Center; 2020 [cited 2018 Feb 20]. Available from: http://www.cancer.go.kr.
  3. National Cancer Center. National Cancer Center & Korea Central Cancer Registry [Internet]. Goyang: National Cancer Center; 2020 [cited 2019 Dec 23]. Available from: https://ncc.re.kr/cancerStatsView.ncc?bbsnum=498&searchKey=total&searchValue=&pageNum=1.
  4. Nkondjock A, Ghadirian P. Risk factors and risk reduction of breast cancer. Med Sci (Paris) 2005; 21(2): 175-180. https://doi.org/10.1051/medsci/2005212175
  5. Morris PG, Hudis CA, Giri D, Morrow M, Falcone DJ, Zhou XK, et al. Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res (Phila) 2011; 4(7): 1021-1029. https://doi.org/10.1158/1940-6207.CAPR-11-0110
  6. Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, et al. Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 2009; 15(8): 2920-2926. https://doi.org/10.1158/1078-0432.CCR-08-2242
  7. Schapira DV, Clark RA, Wolff PA, Jarrett AR, Kumar NB, Aziz NM. Visceral obesity and breast cancer risk. Cancer 1994; 74(2): 632-639. https://doi.org/10.1002/1097-0142(19940715)74:2<632::AID-CNCR2820740215>3.0.CO;2-T
  8. Thune I, Brenn T, Lund E, Gaard M. Physical activity and the risk of breast cancer. N Engl J Med 1997; 336(18): 1269-1275. https://doi.org/10.1056/NEJM199705013361801
  9. Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, Friedman ER, Slingerland JM. Obesity and adverse breast cancer risk and outcome: mechanistic insights and strategies for intervention. CA Cancer J Clin 2017; 67(5): 378-397. https://doi.org/10.3322/caac.21405
  10. Seo JS, Park HA, Kang JH, Kim KW, Cho YG, Hur YI, et al. Obesity and obesity-related lifestyles of Korean breast cancer survivors. Korean J Health Promot 2014; 14(3): 93-102. https://doi.org/10.15384/kjhp.2014.14.3.93
  11. Rooney M, Wald A. Interventions for the management of weight and body composition changes in women with breast cancer. Clin J Oncol Nurs 2007; 11(1): 41-52. https://doi.org/10.1188/07.CJON.41-52
  12. Bhardwaj P, Du B, Zhou XK, Sue E, Harbus MD, Falcone DJ, et al. Caloric restriction reverses obesity-induced mammary gland inflammation in mice. Cancer Prev Res (Phila) 2013; 6(4): 282-289. https://doi.org/10.1158/1940-6207.CAPR-12-0467
  13. Sundaram S, Yan L. Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. Nutr Res 2018; 59: 72-79. https://doi.org/10.1016/j.nutres.2018.07.014
  14. Kim EJ, Choi MR, Park H, Kim M, Hong JE, Lee JY, et al. Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice. Breast Cancer Res 2011; 13(4): R78. https://doi.org/10.1186/bcr2927
  15. Selvakumar P, Badgeley A, Murphy P, Anwar H, Sharma U, Lawrence K, et al. Flavonoids and other polyphenols act as epigenetic modifiers in breast cancer. Nutrients 2020; 12(3): 761. https://doi.org/10.3390/nu12030761
  16. Demark-Wahnefried W, Rogers LQ, Gibson JT, Harada S, Fruge AD, Oster RA, et al. Randomized trial of weight loss in primary breast cancer: impact on body composition, circulating biomarkers and tumor characteristics. Int J Cancer 2020; 146(10): 2784-2796. https://doi.org/10.1002/ijc.32637
  17. Faustino-Rocha A, Oliveira PA, Pinho-Oliveira J, Teixeira-Guedes C, Soares-Maia R, da Costa RG, et al. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. Lab Anim (NY) 2013; 42(6): 217-224. https://doi.org/10.1038/laban.254
  18. LeRoith D, Novosyadlyy R, Gallagher EJ, Lann D, Vijayakumar A, Yakar S. Obesity and type 2 diabetes are associated with an increased risk of developing cancer and a worse prognosis; epidemiological and mechanistic evidence. Exp Clin Endocrinol Diabetes 2008; 116 Suppl 1: S4-S6. https://doi.org/10.1055/s-2008-1081488
  19. Peyrat JP, Bonneterre J, Hecquet B, Vennin P, Louchez MM, Fournier C, et al. Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. Eur J Cancer 1993; 29A(4): 492-497.
  20. Wu W, Ma J, Shao N, Shi Y, Liu R, Li W, et al. Co-targeting IGF-1R and autophagy enhances the effects of cell growth suppression and apoptosis induced by the IGF-1R inhibitor NVP-AEW541 in triple-negative breast cancer cells. PLoS One 2017; 12(1): e0169229. https://doi.org/10.1371/journal.pone.0169229
  21. Porter HA, Perry A, Kingsley C, Tran NL, Keegan AD. IRS1 is highly expressed in localized breast tumors and regulates the sensitivity of breast cancer cells to chemotherapy, while IRS2 is highly expressed in invasive breast tumors. Cancer Lett 2013; 338(2): 239-248. https://doi.org/10.1016/j.canlet.2013.03.030
  22. Gerard C, Brown KA. Obesity and breast cancer - role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue. Mol Cell Endocrinol 2018; 466: 15-30. https://doi.org/10.1016/j.mce.2017.09.014
  23. Kim KJ. Changes of IL-6 and TNF-${\alpha}$ production by macrophages and monocytes after restricted diet and exercise training intervention in diet-induced obese mice. Exer Sci 2010; 19(2): 115-130. https://doi.org/10.15857/KSEP.2010.19.2.115
  24. Cleary MP, Grande JP, Maihle NJ. Effect of high fat diet on body weight and mammary tumor latency in MMTV-TGF-alpha mice. Int J Obes Relat Metab Disord 2004; 28(8): 956-962. https://doi.org/10.1038/sj.ijo.0802664
  25. Zhu Z, Haegele AD, Thompson HJ. Effect of caloric restriction on pre-malignant and malignant stages of mammary carcinogenesis. Carcinogenesis 1997; 18(5): 1007-1012. https://doi.org/10.1093/carcin/18.5.1007
  26. Brown KA, McInnes KJ, Hunger NI, Oakhill JS, Steinberg GR, Simpson ER. Subcellular localization of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 provides a link between obesity and breast cancer in postmenopausal women. Cancer Res 2009; 69(13): 5392-5399. https://doi.org/10.1158/0008-5472.CAN-09-0108
  27. Cleary MP, Hu X, Grossmann ME, Juneja SC, Dogan S, Grande JP, et al. Prevention of mammary tumorigenesis by intermittent caloric restriction: does caloric intake during refeeding modulate the response? Exp Biol Med (Maywood) 2007; 232(1): 70-80.
  28. Rogozina OP, Bonorden MJ, Seppanen CN, Grande JP, Cleary MP. Effect of chronic and intermittent calorie restriction on serum adiponectin and leptin and mammary tumorigenesis. Cancer Prev Res (Phila) 2011; 4(4): 568-581. https://doi.org/10.1158/1940-6207.CAPR-10-0140
  29. Rogozina OP, Nkhata KJ, Nagle EJ, Grande JP, Cleary MP. The protective effect of intermittent calorie restriction on mammary tumorigenesis is not compromised by consumption of a high fat diet during refeeding. Breast Cancer Res Treat 2013; 138(2): 395-406. https://doi.org/10.1007/s10549-013-2464-7
  30. Cleary MP, Grossmann ME. The manner in which calories are restricted impacts mammary tumor cancer prevention. J Carcinog 2011; 10(1): 21. https://doi.org/10.4103/1477-3163.85181
  31. Friedenreich CM, Woolcott CG, McTiernan A, Ballard-Barbash R, Brant RF, Stanczyk FZ, et al. Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women. J Clin Oncol 2010; 28(9): 1458-1466. https://doi.org/10.1200/JCO.2009.24.9557
  32. Baracos VE, Martin L, Korc M, Guttridge DC, Fearon KC. Cancer-associated cachexia. Nat Rev Dis Primers 2018; 4(1): 17105. https://doi.org/10.1038/nrdp.2017.105
  33. Du J, Chen GG, Vlantis AC, Chan PK, Tsang RK, van Hasselt CA. Resistance to apoptosis of HPV 16-infected laryngeal cancer cells is associated with decreased Bak and increased Bcl-2 expression. Cancer Lett 2004; 205(1): 81-88. https://doi.org/10.1016/j.canlet.2003.09.035
  34. Barisic K, Petrik J, Rumora L. Biochemistry of apoptotic cell death. Acta Pharm 2003; 53(3): 151-164.
  35. Antonsson B, Martinou JC. The Bcl-2 protein family. Exp Cell Res 2000; 256(1): 50-57. https://doi.org/10.1006/excr.2000.4839
  36. Schreiber V, Dantzer F, Ame JC, de Murcia G. Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 2006; 7(7): 517-528. https://doi.org/10.1038/nrm1963
  37. Escrich R, Costa I, Moreno M, Cubedo M, Vela E, Escrich E, et al. A high-corn-oil diet strongly stimulates mammary carcinogenesis, while a high-extra-virgin-olive-oil diet has a weak effect, through changes in metabolism, immune system function and proliferation/apoptosis pathways. J Nutr Biochem 2019; 64: 218-227. https://doi.org/10.1016/j.jnutbio.2018.11.001
  38. Yan L, Sundaram S, Mehus AA, Picklo MJ. Time-restricted feeding attenuates high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma in mice. Anticancer Res 2019; 39(4): 1739-1748. https://doi.org/10.21873/anticanres.13280