J Breast Cancer.  2013 Jun;16(2):164-170. 10.4048/jbc.2013.16.2.164.

Enhancing the Effects of Low Dose Doxorubicin Treatment by the Radiation in T47D and SKBR3 Breast Cancer Cells

Affiliations
  • 1Department of Medical Physics, Tabriz University of Medical Sciences School of Medicine, Tabriz, Iran. pirayeshj@gmail.com
  • 2Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 3Department of Radiology and Radiotherapy, Imam Reza Medical Center for Treatment and Training, Tabriz, Iran.
  • 4Department of Biostatistics, Tabriz University of Medical Sciences School of Health & Nutrition, Tabriz, Iran.

Abstract

PURPOSE
Breast cancer is the most common malignancy of women worldwide. Radiotherapy consists of a vital element in the treatment of breast cancer but relative side effects and different radioactive responses are limiting factors for a successful treatment. Doxorubicin has been used to treat cancers for over 30 years and is considered as the most effective drug in the treatment of breast cancer. There are also many chronic side effects that limit the amount of doxorubicin that can be administered. The combined radio-drug treatment, with low doses, can be an approach for reducing side effects from single modality treatments instead of suitable cure rates.
METHODS
We have studied the effect of 1, 1.5, and 2 Gy doses of 9 MV X-rays along with 1 microM doxorubicin on inducing cell death, apoptosis and also p53 and PTEN gene expression in T47D and SKBR3 breast cancer cells.
RESULTS
Doxorubicin treatment resulted in upregulation of radiation-induced levels of p53 and downregulation of PTEN at 1 and 1.5 Gy in T47D breast cancer cells, as well as downregulation of p53 mRNA level of expression and upregulation of PTEN mRNA level of expression in SKBR3 breast cancer cell line. In addition, doxorubicin in combination with radiation decreased the viability of breast cancer cell lines in the both cell lines.
CONCLUSION
Low doses of doxorubicin, with least cell toxicity, may be an effective treatment for breast cancer when used in conjunction with ionizing radiation.

Keyword

Breast neoplasms; Cell line; Combined modality therapy; Doxorubicin; Ionizing radiation

MeSH Terms

Apoptosis
Breast
Breast Neoplasms
Cell Death
Cell Line
Combined Modality Therapy
Down-Regulation
Doxorubicin
Female
Gene Expression
Humans
Radiation, Ionizing
RNA, Messenger
Up-Regulation
Doxorubicin
RNA, Messenger

Figure

  • Figure 1 Effect of irrdiation alone and in combination with doxorubicin on viability of T47D (A) and SKBR3 (B) cells. The cells were treated with 1 µM doxorubicin and irradiated with doses of 100, 150, and 200 cGy. IR=irradiation; DOX=doxorubicin.

  • Figure 2 Viability of T47D and SKBR3 cell lines following combined treatment with 1 µM doxorubicin and 100,150, 200 cGy irradiation. IR=irradiation; DOX=doxorubicin.


Reference

1. Moulder S, Hortobagyi GN. Advances in the treatment of breast cancer. Clin Pharmacol Ther. 2008; 83:26–36.
Article
2. Hollestelle A, Elstrodt F, Nagel JH, Kallemeijn WW, Schutte M. Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines. Mol Cancer Res. 2007; 5:195–201.
Article
3. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994; 73:2013–2026.
Article
4. Sinthupibulyakit C, Grimes KR, Domann FE, Xu Y, Fang F, Ittarat W, et al. p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose. Int J Oncol. 2009; 35:609–615.
Article
5. Spitz DR, Sim JE, Ridnour LA, Galoforo SS, Lee YJ. Glucose deprivation-induced oxidative stress in human tumor cells. A fundamental defect in metabolism? Ann N Y Acad Sci. 2000; 899:349–362.
Article
6. Kaabinejadian S, Fouladdel SH, Ramezani M, Azizi E. p53 expression in MCF7, T47D and MDA-MB 468 breast cancer cell lines treated with adriamycin using RT-PCR and immunocytochemistry. J Biol Sci. 2008; 8:380–385.
Article
7. Schwarz SB, Schaffer PM, Kulka U, Ertl-Wagner B, Hell R, Schaffer M. The effect of radio-adaptive doses on HT29 and GM637 cells. Radiat Oncol. 2008; 3:12.
Article
8. Feki A, Irminger-Finger I. Mutational spectrum of p53 mutations in primary breast and ovarian tumors. Crit Rev Oncol Hematol. 2004; 52:103–116.
Article
9. Putti TC, El-Rehim DM, Rakha EA, Paish CE, Lee AH, Pinder SE, et al. Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis. Mod Pathol. 2005; 18:26–35.
Article
10. Angeloni SV, Martin MB, Garcia-Morales P, Castro-Galache MD, Ferragut JA, Saceda M. Regulation of estrogen receptor-alpha expression by the tumor suppressor gene p53 in MCF-7 cells. J Endocrinol. 2004; 180:497–504.
Article
11. Soussi T, Béroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer. 2001; 1:233–240.
Article
12. Miller LD, Smeds J, George J, Vega VB, Vergara L, Ploner A, et al. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci U S A. 2005; 102:13550–13555.
Article
13. Liu W, Konduri SD, Bansal S, Nayak BK, Rajasekaran SA, Karuppayil SM, et al. Estrogen receptor-alpha binds p53 tumor suppressor protein directly and represses its function. J Biol Chem. 2006; 281:9837–9840.
Article
14. Carter SK. C.R.O.S. conference on combined modalities chemotherapy/radiotherapy. Hilton Head Island, South Carolina, November 15-18, 1978. Cancer Chemother Pharmacol. 1979; 2:139–142.
15. Tan ML, Choong PF, Dass CR. Review: doxorubicin delivery systems based on chitosan for cancer therapy. J Pharm Pharmacol. 2009; 61:131–142.
Article
16. O'Shaughnessy J. Liposomal anthracyclines for breast cancer: overview. Oncologist. 2003; 8:Suppl 2. 1–2.
17. Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007; 608:1–22.
Article
18. Bergh J, Jönsson PE, Glimelius B, Nygren P. SBU-group. Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in breast cancer. Acta Oncol. 2001; 40:253–281.
19. Hortobágyi GN. Anthracyclines in the treatment of cancer. An overview. Drugs. 1997; 54:Suppl 4. 1–7.
20. Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984; 226:466–468.
Article
21. Gatti L, Zunino F. Overview of tumor cell chemoresistance mechanisms. Methods Mol Med. 2005; 111:127–148.
Article
22. Chabner BA, Ryan DP, Paz-Ares L, Garcia-Carbonero R, Calabresi P. Antineoplastic agents. In : Hardman JG, Lmbird LE, Gilman A, editors. Goodman & Gilman's the Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill;2001. p. 1389–1399.
23. Chanan-Khan A, Srinivasan S, Czuczman MS. Prevention and management of cardiotoxicity from antineoplastic therapy. J Support Oncol. 2004; 2:251–256.
24. Meek DW. The p53 response to DNA damage. DNA Repair (Amst). 2004; 3:1049–1056.
Article
25. Nakamura Y. Isolation of p53-target genes and their functional analysis. Cancer Sci. 2004; 95:7–11.
Article
26. Lu X, Nannenga B, Donehower LA. PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 2005; 19:1162–1174.
Article
27. Ju GZ, Shen B, Sun SL, Yan FQ, Fu SB. Effect of X-rays on expression of caspase-3 and p53 in EL-4 cells and its biological implications. Biomed Environ Sci. 2007; 20:456–459.
28. Sasaki A, Udaka Y, Tsunoda Y, Yamamoto G, Tsuji M, Oyamada H, et al. Analysis of p53 and miRNA expression after irradiation of glioblastoma cell lines. Anticancer Res. 2012; 32:4709–4713.
29. Zhuang HQ, Wang J, Yuan ZY, Zhao LJ, Wang P, Wang CL. The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro. J Exp Clin Cancer Res. 2009; 28:123.
Article
Full Text Links
  • JBC
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr