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Volume 10

Journal of Cancer Science & Therapy

ISSN: 1948-5956

Euro Cancer 2018

July 23-25, 2018

July 23-25, 2018 | Rome, Italy

Euro-Global Summit on

Cancer Therapy & Radiation Oncology

Through which pathway does trastuzumab and miR-122-5p combinatorial administration lead

breast cancer cells to apoptosis: Intrinsic or extrinsic pathway?

Sercan Ergun

Ordu University, Turkey

Statement of the Problem:

In most of breast cancer cells, HER2 receptors are known to be cleaved by an ectodomain sheddase,

ADAM10, to liberate HER2 extracellular domain (ECD). This provides ligand-independent growth to breast cancer cells and

trastuzumab, anti-HER2 agent, cannot inactivate HER2 by binding ECD portion of it. In our previous studies, we found that

miR-122-5p, miRNA targeting ADAM10, and trastuzumab combinatorial administration to HER2-positive breast cancer cell

line, SKBR3, increases the efficiency of trastuzumab by leading SKBR3 cells to apoptosis more through blocking the sheddase

activity of ADAM10 on HER2. The aim of this study is to display that miR-122-5p, together with trastuzumab, leads SKBR3 cells

apoptosis by which pathway: intrinsic or extrinsic.

Methodology & Theoretical Orientation:

SKBR3 cells were first transfected with the miR-122-5p mimic for 48 hours. Then,

0.5 μM trastuzumab was applied to miR-122-5p-transfected SKBR3 cells and non-transfected SKBR3 cells for 24 hours. Next,

the expression levels of CASP3,

CASP8

and

CASP9

genes, which are key molecules in apoptotic pathway, were examined by

real-time PCR.

Findings:

Expression levels of

CASP3

and

CASP8

, but not

CASP9

, increased significantly in miR-122-5p-transfected

Trastuzumab-administered SKBR3 cells when compared to non-miR-122-5p transfected Trastuzumab-administered SKBR3

cells. A significant increase in the expression level of

CASP8

with

CASP3

showed apoptosis to be activated via extrinsic pathway

(instead of the mitochondrial intrinsic pathway regulated by

CASP9

) with the effect of miR-122-5p in trastuzumab-administered

SKBR3 cells.

Conclusion & Significance:

Consequently, the apoptosis enhancing effect of trastuzumab and miR-122-5p combinatorial

administration through extrinsic pathway may be presented as a new treatment option for HER2+ breast cancer.

Figure 1:

Comparison of expression levels of

CASP3, 8, 9

genes between SKBR3 cells administered with trastuzumab and trastuzumab + miR-122-5p-mimic.

Recent Publications:

1. Ergun S, et al. (2014) Expression patterns of miR-221 and its target caspase-3 in different cancer cell lines. Mol Biol

Rep. 41:5877–5881.

2. Wang B, et al. (2012) MiR-122 inhibits cell proliferation and tumorigenesis of breast cancer by targeting IGF1R. PLoS

One 7(10):e47053.

3. Pollack M and Leeuwenburgh C (2001) Apoptosis and aging: role of the mitochondria. J Gerontol A Biol Sci Med Sci.

56(11):B475–B482.

Sercan Ergun, J Cancer Sci Ther 2018, Volume 10

DOI: 10.4172/1948-5956-C8-144