Morphological Changes of Cisplatin-resistant Human Breast Cancer MCF-7 Cell Line

Nanda Ayu Puspita, Amy Bedford

Abstract


Objective: To evaluate morphological changes of breast cancer cell line MCF-7 following the development of acquired resistance towards cisplatin. Resistance towards anticancer agents still plays an important role in the breast cancer chemotherapy failure.

Methods: The cisplatin resistant subline MCF-7/CisR was developed in-vitro by cultivating the parental cell line cisplatin-sensitive MCF-7 with raising concentration of cisplatin (from 0.01 to 2.3 µM) for four months. The cell morphology was observed by giemsa staining.

Results: The resistance was shown by the increase of IC50 by 9 folds on MCF-7/CisR compared to the initial IC50 value of MCF-7. The change in cisplatin cytotoxic potency on the resistant cell line was accompanied by the morphological modification, including the enlargement of cell size, the increase of nucleus and cytoplasm ratio, and the increase of the number of microvesicular and cytoplasmic granules.

Conclusions: This result has supported the underlying mechanism of cisplatin resistance, including the ability of the cells to decrease intracellular cisplatin concentration and repair DNA damage effects.

Keywords: Drug resistance, human breast cancer, cisplatin, MCF-7

 

DOI: 10.15850/ijihs.v5n1.960


Keywords


Drug resistance, human breast cancer, cisplatin, MCF-7

Full Text:

PDF

References


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):1–22.

Sun H , Jia J, Wang X, Ma B, Di L, Song G, et al. CD44+/CD24− breast cancer cells isolated from MCF-7 cultures exhibit enhanced angiogenic properties. Clin Translational Oncol. 2013;15(1):46–54.

WHO. Breast cancer: prevention and control. [cited 2011 Nov 1]. Available from: http://www.who.int/cancer/detection/breastcancer/en/index1.html.

Florea AM, Büsselberg D. Breast cancer and possible mechanisms of therapy resistance. J Local Global Health Sci. 2013;2(2):2.

Lukyanova NY, Rusetskya NV, Tregubova NA, Chekhun VF. Molecular profile and cell cycle in MCF-7 cells resistant to cisplatin and doxorubicin. Exp Oncol. 2009;31(2):87–91.

Meijera C, van Luyn MJA, Nienhuis EF, Blom N, Mulder NH, de Vries EGE, et al. Ultrastructural morphology and localisation of cisplatin-induced platinum–DNA adducts in a cisplatin-sensitive and -resistant human small cell lung cancer cell line using electron microscopy. Biochem Pharmacol. 2001;61(5):573–8.

Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;5(1):364–78.

Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Pérez JM. Biochemical mechanisms of cisplatin cytotoxicity. Anti-Cancer Agents Medicinal Chem. 2007;7(1):3–18.

Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003;22(47):7265–79.

Byrski T, Huzarski T, Dent R, Marczyk E, Jasiowka M, Gronwald J, et al. Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast cancer research and treatment.2014;147(2): 401–5.

McDermott M, Eustace AJ, Busschots S, Breen L, Crown J, Clynes M, et al. In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: a practical guide with case studies. Frontier Oncol. 2015;4(40):32–48.

Rebucci M, Michiels C. Molecular aspects of cancer cell resistance to chemotherapy. Biochem Pharmacol. 2013;85(9):1219–26.

Mao Q, Unadkat JD, Role of the (BCRP/ABCG2) in drug transport--an update. AAPS J. 2015;17(1):65–82.

Lloyd AC. The regulation of cell size. Cell. 2013;154(6):1194–205.

Dickson MA, Schwartz GK. Development of cell cycle inhibitors for cancer therapy. Curr Oncol. 2009;16(2):36–43.

Bucher N, Britten C. G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer. Br J Cancer. 2008;98(3):523–8.

Lazebnik Y. What are the hallmarks of cancer? Nat Rev Cancer. 2010;10(4):232–33.

LaPensee EW, Ben-Jonathan N. Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy. Endocrine-related Cancer. 2010;17(2): R91–107.

D’Anselmi F, Valerio M, Cucina A, Galli L, Proietti S, Dinicola S, et al. Metabolism and cell shape in cancer: a fractal analysis. Int J Biochem Cell Biol. 2011;43(7):1052–8.

Pasqualato A, Palombo A, Cucina A, Mariggiò MA, Galli L, Passaro D, et al. Quantitative shape analysis of chemoresistant colon cancer cells: correlation between morphotype and phenotype. Exp Cell Res. 2012;318(7):835–46.


Refbacks

  • There are currently no refbacks.




This journal indexed by:

             

  

Creative Commons License
IJIHS is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License



View My Stats