Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 1

592 - Effects of novel targeted anticancer drugs on cytotoxicity, apoptosis, angiogenesis, EMT, drug resistance and autophagic mechanism

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Basic Science

Tumour Site

Presenters

Seyma Aydinlik

Citation

Annals of Oncology (2019) 30 (suppl_5): v1-v24. 10.1093/annonc/mdz238

Authors

S. Aydinlik1, A. Uvez2, E.I. Armutak3, E. Dere1, E. Ulukaya4

Author affiliations

  • 1 Molecular Biology, Uludag University, 16059 - Bursa/TR
  • 2 Histology And Embryology, Istanbul University, 34010 - Istanbul/TR
  • 3 Histology And Embryology,, Istanbul University, 34010, - Istanbul/TR
  • 4 Medical Biochemistry, Istinye University, 34010 - Istanbul/TR

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 592

Background

Metastatic colon cancer has a survival rate less than %5 despite the use of effective chemotherapeutic regimen. Prognostic and predictive importance of EGFR is still contradictive in colon cancer. Tyrosine kinase inhibitor canertinib was used in this study to block the EGFR receptor. The effect of Palladium (Pd) (II) compound [PdCl(terpy)](sac).2H2O] and canertinib combination treatment was investigated in this study. 5-fluorouracil (5-FU), a chemotherapeutic drug was used as positive control.

Methods

The cytotoxic effects of the combination of Pd (II)+canertinib and the 5-FU+canertinib combination on colon cancer cell line (HCT-15, HT-29) were determined by the SRB test. Apoptosis, the acidic vesiculations, mitochondrial depolarization were determined by flow cytometry, Annexin-V-Cy3/SYTOX, acridine orange, JC-1 staining. Alterations in proteins related to EGFR-associated pathway, EMT, apoptosis/autophagy and drug carrier were evaluated by western blot. Invasion, wound healing and colony forming ability were determined. Tube forming in HUVEC and vessel forming ability was assessed by matrigel and CAM test respectively.

Results

A significant decrease in p-ERK, p-P38, p-EGFR protein levels was observed with EGFR inhibition, while the cell viability was decreased. Cell death was determined as mitochondrial apoptosis. LC3-II, Beclin-1, Atg5 protein levels, and increased acidic vesicles and decreased p-MTOR protein levels were associated with increased autophagy in combination therapy. In addition, increased E-cadherin expression and decreased N-cadherin, fibronectin and vimentin expression related to decrease in invasion, migration, and colony forming ability. ROS expression and DNA damage increased. Significant differences in MDR-1 and MRP-1 protein levels were observed with EGFR inhibition. In addition, the ability to create tubes and vessels has decreased significantly.

Conclusions

EGFR inhibition along with Pd(II) has been shown to increased cytotoxicity, decreased invasion, migration and vessel formation abilities. Furthermore, induced ROS levels and increased autophagic signaling are found to be necessary for mitochondria-dependent apoptosis in colon cancer cells.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Uludag University.

Funding

Scientific Research Projects Foundation (BAP) of Uludag University of Turkey [Project No. (DDP(F)-2017)].

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.