654 - Antitumor and antiangiogenic activity of sorafenib on colorectal cancer

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Saadettin Kilickap
Authors S. Kilickap1, A. Altun2, N.A. Babacan1, H. Ataseven3, T. Kaya2
  • 1Medical Oncology, Cumhuriyet University Faculty of Medicine, Sivas/TR
  • 2Pharmacology, Cumhuriyet University Faculty of Medicine, Sivas/TR
  • 3Gastroenterology, Cumhuriyet University Faculty of Medicine, Sivas/TR

Abstract

Background

Addition to standard chemotherapy regimens of targeted biological agents such as bevacizumab and cetuximab has led to improved outcomes in colorectal cancer (CRC). We aimed to investigate antitumoral and antiangiogenic (AAG) effects of sorafenib (SRF) in CRC cells.

Methods

The effect on proliferation of SRF was evaluated by using real-time cell analysis system (xCELLigence) in DLD-1 CRC cells. After the optimal seeding concentration for proliferation of the DLD-1 was determined, the cells were exposed to 10 µL of medium containing SRF 200 mg (500, 250, 125, 62.5, 31.25, 15.62, 7.81, 3.9, 1.95, 0.97 and 0.48 nM/well). Controls received either medium only, or medium + SRF with a final concentration of 500 nM. The effects of SRF on angiogenesis were studied with chorioallantoic membrane (CAM) model. Angiogenesis was evaluated by using Burgermeister's scoring system.

Results

We used the 40,000 cells/well concentration in the xCELLigence assay to examine the antiproliferative effect elicited by SRF, as the concentration displayed the lowest variation. SRF treated DLD-1 cells exhibited decreasing cell index values in a concentration-dependent manner. 500, 250, 125, 62.5 and 31.5 nM SRF caused statistically significant cytotoxic effect on DLD-1 cells. There was no a significantly difference between these concentrations. Also, 15.6 and 7.8 nM SRF led to cytotoxic effect, but these effects were significantly lower than the 500, 250, 125, 62.5 and 31.5 nM SRF. The cytotoxic effect of SRF on DLD-1 cells gradually diminished with decreasing concentrations (p < 0,001). At 24-hours after treatment with SRF, an IC50 value of (IC50) 1.26x10−9 M was achieved. The eggs on which a 10 µl-agarose pellet with no drug was installed demonstrated no significant AAG effect (average AAG score = 0.1). The AAG effect of SRF compared with bevacizumab and negative control. The AAG effects of the drugs were similar and higher compared to the negative control (p < 0.05). AAG scores of SRF in 100, 10 and 1 nM concentrations were 1.05, 0.75, and 0.55, respectively. The AAG effect on CAM of SRF was dose-dependent. The AAG score with the 100 nM was significantly higher than 1 nM (p = 0.043).

Discussion

SRF has antitumor and AAG effects on human colorectal cancer cell line. These effects have positively correlated with its concentration.

Disclosure

All authors have declared no conflicts of interest.