Skip to main content
SpringerLink
Log in

Trace Elements and Chemotherapy Sensitivity

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Trace elements might be associated with the development of hepatocellular carcinoma (HCC) and the efficacy of chemotherapy against HCC. Therefore, this study aimed to explore the association between trace elements and efficacy of chemotherapy in patients with HCC. Cancer, cancer-adjacent, and cancer-free tissues were collected intraoperatively from 55 patients with HCC between January 2001 and April 2004 at the Affiliated Tumor Hospital of Guangxi Medical University in Guangxi (China), a high HCC incidence area in the world. Trace element levels were analyzed by atomic absorption spectrophotometry. In vitro sensitivity of cancer cells to five chemotherapeutic drugs (5-fluorouracil, doxorubicin, cisplatin, carboplatin, and mitomycin) was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in cancer cells from 32 patients. Zinc, copper, manganese, and selenium levels had the same gradient distribution in different liver tissues: cancer < cancer-adjacent < cancer-free tissues. Copper levels of cancer tissues were negatively correlated with body weight (r = −0.278, P = 0.027), while manganese and selenium levels were negatively correlated with age (r = −0.297, P = 0.015; r = −0.285, P = 0.018, respectively). Simple correlation analyses revealed that the carboplatin sensitivity was negatively correlated with selenium levels of cancer tissues, while doxorubicin sensitivity was negatively correlated with manganese levels (r = −0.497, P = 0.004). Partial correlation analyses showed that doxorubicin sensitivity only was negatively correlated with manganese levels (r = −0.450, P = 0.014). These results suggest that the selenium and manganese content in primary HCC tissues could influence the response of the HCC cells to carboplatin and doxorubicin. These preliminary results provide a basis for future studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kohler BA, Ward E, McCarthy BJ, Schymura MJ, Ries LA, Eheman C, Jemal A, Anderson RN, Ajani UA, Edwards BK (2011) Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst 103(9):714–736. doi:10.1093/jnci/djr077

    Article  PubMed  PubMed Central  Google Scholar 

  2. Centers for Disease Control Prevention (2010) Hepatocellular carcinoma—United States, 2001-2006. MMWR Morb Mortal Wkly Rep 59(17):517–520

    Google Scholar 

  3. Altekruse SF, McGlynn KA, Reichman ME (2009) Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 27(9):1485–1491. doi:10.1200/JCO.2008.20.7753

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zhang CY, Huang TR, Yu JH, Zhang ZQ, Li JL, Deng W, Ye SY, Zhou DN, He ZF (2010) Epidemiological analysis of primary liver cancer in the early 21st century in Guangxi province of China. Chin J Cancer 29(5):545–550

    Article  PubMed  Google Scholar 

  5. Van Rensburg SJ, Cook-Mozaffari P, Van Schalkwyk DJ, Van der Watt JJ, Vincent TJ, Purchase IF (1985) Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei. Br J Cancer 51(5):713–726

    Article  PubMed  PubMed Central  Google Scholar 

  6. Devita VT Jr, Lawrence TS, Rosenberg SA (eds) (2011) Cancer of the liver. In: Cancer Principles & Practice of Oncology. Philadelphia, Lippincott Williams & Wilkins, USA, pp 997–1001

  7. Cheng WH (2009) Impact of inorganic nutrients on maintenance of genomic stability. Environ Mol Mutagen 50(5):349–360. doi:10.1002/em.20489

    Article  CAS  PubMed  Google Scholar 

  8. Tashiro H, Kawamoto T, Okubo T, Koide O (2003) Variation in the distribution of trace elements in hepatoma. Biol Trace Elem Res 95(1):49–63. doi:10.1385/BTER:95:1:49

    Article  CAS  PubMed  Google Scholar 

  9. Maeda T, Shimada M, Harimoto N, Tsujita E, Maehara S, Rikimaru T, Tanaka S, Shirabe K, Maehara Y (2005) Role of tissue trace elements in liver cancers and non-cancerous liver parenchyma. Hepato-Gastroenterology 52(61):187–190

    CAS  PubMed  Google Scholar 

  10. Jin J, Hao. S, Yu HX, Yao HY, Mao J, Wang CJ, Yang MJ, Mi Y (2007) Evaluation of Cu in hepatocellular carcinoma by particle induced X-ray emission. J Trace Elem Med Biol 21(4):255–260. doi:10.1016/j.jtemb.2007.06.004

    Article  CAS  Google Scholar 

  11. Balter V, Nogueira da Costa A, Bondanese VP, et al. (2015) Natural variations of copper and sulfur stable isotopes in blood of hepatocellular carcinoma patients. Proc Natl Acad Sci U S A 112(4):982–985. doi:10.1073/pnas.1415151112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bruix J, Sherman M, American Association for the Study of Liver D (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022. doi:10.1002/hep.24199

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lopez PM, Villanueva A, Llovet JM (2006) Systematic review: evidence-based management of hepatocellular carcinoma—an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 23(11):1535–1547. doi:10.1111/j.1365-2036.2006.02932.x

    Article  CAS  PubMed  Google Scholar 

  14. Tobey RA, Tesmer JG (1985) Differential response of cultured human normal and tumor cells to trace element-induced resistance to the alkylating agent melphalan. Cancer Res 45(6):2567–2571

    CAS  PubMed  Google Scholar 

  15. Ivanova D, Bakalova R, Lazarova D, Gadjeva V, Zhelev Z (2013) The impact of reactive oxygen species on anticancer therapeutic strategies. Adv Clin Exp Med 22(6):899–908

    PubMed  Google Scholar 

  16. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13. doi:10.1042/BJ20081386

    Article  CAS  PubMed  Google Scholar 

  17. Chinese Society of Liver Cancer (2000) The diagnostic criteria of primary liver cancer. Chin J Hepatol 8:135

    Google Scholar 

  18. Tang D, Wei C (1995) MTT assay as a method of determining the chemosensitivity in human primary hepatocellular carcinoma. Pract J Cancer 10:14–15

    Google Scholar 

  19. Sargent JM, Taylor CG (1989) Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia. Br J Cancer 60(2):206–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Elmberg M, Hultcrantz R, Ekbom A, et al. (2003) Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology 125(6):1733–1741

    Article  PubMed  Google Scholar 

  21. Kumagi T, Horiike N, Michitaka K, et al. (2004) Recent clinical features of Wilson’s disease with hepatic presentation. J Gastroenterol 39(12):1165–1169. doi:10.1007/s00535-004-1466-y

    Article  PubMed  Google Scholar 

  22. Wang YX, Qin JF, Wu SM, Yan LB (1990) Study on the relation of Se, Mn, Fe, Sr, Pb, Zn, Cu, and Ca to liver cancer mortality from analysis of scalp hair. Sci Total Environ 91:191–198

    Article  CAS  PubMed  Google Scholar 

  23. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2004) Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364(9441):1219–1228. doi:10.1016/S0140-6736(04)17138-9

    Article  CAS  PubMed  Google Scholar 

  24. Liaw KY, Lee PH, Wu FC, Tsai JS, Lin-Shiau SY (1997) Zinc, copper, and superoxide dismutase in hepatocellular carcinoma. Am J Gastroenterol 92(12):2260–2263

    CAS  PubMed  Google Scholar 

  25. Yang CS (2000) Vitamin nutrition and gastroesophageal cancer. J Nutr 130(2S Suppl):338S–339S

    CAS  PubMed  Google Scholar 

  26. Lu H, Cai L, Mu LN, et al. (2006) Dietary mineral and trace element intake and squamous cell carcinoma of the esophagus in a Chinese population. Nutr Cancer 55(1):63–70. doi:10.1207/s15327914nc5501_8

    Article  PubMed  Google Scholar 

  27. Yu MW, Horng IS, Hsu KH, Chiang YC, Liaw YF, Chen CJ (1999) Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. Am J Epidemiol 150(4):367–374

    Article  CAS  PubMed  Google Scholar 

  28. Geybels MS, Verhage BA, van Schooten FJ, van den Brandt PA (2012) Measures of combined antioxidant and pro-oxidant exposures and risk of overall and advanced stage prostate cancer. Ann Epidemiol 22(11):814–820. doi:10.1016/j.annepidem.2012.07.010

    Article  PubMed  Google Scholar 

  29. Kristal AR, Darke AK, Morris JS, et al. (2014) Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk. J Natl Cancer Inst 106(3):djt456. doi:10.1093/jnci/djt456

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kenfield SA, Van Blarigan EL, DuPre N, Stampfer MJ, Giovannucci EL, Chan JM (2015) Selenium supplementation and prostate cancer mortality. J Natl Cancer Inst 107(1):360. doi:10.1093/jnci/dju360

    Article  PubMed  Google Scholar 

  31. Calvo FB, Santos Junior D, Rodrigues CJ, Krug FJ, Marumo JT, Schor N, Bellini MH (2009) Variation in the distribution of trace elements in renal cell carcinoma. Biol Trace Elem Res 130(2):107–113. doi:10.1007/s12011-009-8325-x

    Article  CAS  PubMed  Google Scholar 

  32. Leung TW, Patt YZ, Lau WY, et al. (1999) Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma. Clin Cancer Res 5(7):1676–1681

    CAS  PubMed  Google Scholar 

  33. Yeo W, Mok TS, Zee B, et al. (2005) A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst 97(20):1532–1538. doi:10.1093/jnci/dji315

    Article  CAS  PubMed  Google Scholar 

  34. Su Y (2014) Cancer chemosensitivity testing: review. J Cancer Ther 5:672–679

    Article  Google Scholar 

  35. Burstein HJ, Mangu PB, Somerfield MR, Schrag D, Samson D, Holt L, Zelman D, Ajani JA, American Society of Clinical O (2011) American Society of Clinical Oncology clinical practice guideline update on the use of chemotherapy sensitivity and resistance assays. J Clin Oncol 29(24):3328–3330. doi:10.1200/JCO.2011.36.0354

    Article  PubMed  Google Scholar 

  36. Ortega R, Moretto P, Fajac A, Benard J, Llabador Y, Simonoff M (1996) Quantitative mapping of platinum and essential trace metal in cisplatin resistant and sensitive human ovarian adenocarcinoma cells. Cell Mol Biol (Noisy-Le-Grand) 42(1):77–88

    CAS  Google Scholar 

  37. Raso E, Paku S, Kopper L, Timar J (2003) Trace elements improve survival of DTIC-treated mice with overt liver metastases of Lewis lung carcinoma. Pathol Oncol Res 9(2):96–99

    Article  CAS  PubMed  Google Scholar 

  38. Yu SY, Zhu YJ, Li WG (1997) Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biol Trace Elem Res 56(1):117–124

    Article  CAS  PubMed  Google Scholar 

  39. Yu SY, Zhu YJ, Li WG, Huang QS, Huang CZ, Zhang QN, Hou C (1991) A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China. Biol Trace Elem Res 29(3):289–294

    Article  CAS  PubMed  Google Scholar 

  40. Meplan C, Hesketh J (2012) The influence of selenium and selenoprotein gene variants on colorectal cancer risk. Mutagenesis 27(2):177–186. doi:10.1093/mutage/ger058

    Article  CAS  PubMed  Google Scholar 

  41. Brodska B, Holoubek A (2011) Generation of reactive oxygen species during apoptosis induced by DNA-damaging agents and/or histone deacetylase inhibitors. Oxidative Med Cell Longev 2011:253529. doi:10.1155/2011/253529

    Article  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the help of the technicians of the pathology department of The Affiliated Tumor Hospital of Guangxi Medical University. The authors thank the patients for their invaluable participation. This study was funded by the Guangxi Natural Science Fund (No. 2010GXNSFA 013243001).

Author information

Authors and Affiliations

  1. The First Chemotherapy Department, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China

    Zhihui Liu

  2. Department of ultrasonography, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China

    Weiping Yang

  3. Guangxi Center of Analysis and Test Research, Nanning, Guangxi Province, 530022, China

    Gang Long

  4. Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China

    Changyuan Wei

Authors
  1. Zhihui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiping Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gang Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Changyuan Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Changyuan Wei.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the hospital Ethics Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of Interest

The authors declare that they have no competing interests.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Z., Yang, W., Long, G. et al. Trace Elements and Chemotherapy Sensitivity. Biol Trace Elem Res 173, 283–290 (2016). https://doi.org/10.1007/s12011-016-0667-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-016-0667-6

Keywords

Search

Navigation