C6-Ceramide (C6-Cer) to Induce Sensitivity to Cetuximab (Cet) in KRAS Mutant Colorectal Cancer (Crc)

Menendez A, Haidemenos G, Curzake D, Luo L and Wanebo H

Hematology and Medical Oncology, Indiana University School of Medicine, USA
Department of Medicine, Roger Williams Medical Center, USA
University of Rhode Island College of Pharmacy, USA
Division of Surgical Oncology, Landmark Medical Center, USA

^*Correspondance to: Harold Wanebo 

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Abstract:

Background: Cet is beneficial for patients with metastatic KRAS Wild type (WT) CRC. C6-Cer can act synergistically with chemotherapy to induce apoptosis. The aim was to compare growth inhibition percentage (GIP) of cytostatics 5-FU, oxaliplatin (Ox) and Cet with or without C6-Cer in KRAS WT and KRAS mutant (KRAS Mut) CRC cell lines (SW48 and SW480, respectively).
Methods: Cells were incubated with IC50 (0.8μM for 5-FU, 0.04μM for Ox, 25 μg/mL for Cet, and C6-Cer concentrations ranged from 5 to 10 μM). Cell survival was assessed 72h after using 0.4% Trypan Blue.
Results: C6-Cer’s GIP was 78.3% for SW-480 (vs. 33.33% for SW-48). Addition of C6-Cer increased GIP with an especially significant effect on SW-480. Addition of 5 and 7.5μM resulted in GIP of 75% and 86.25%, respectively, vs. 32.5% of 5-FU + Ox + Cet alone. The greatest effect was seen when 10μM of C6-Cer was added (92.5%). Same concentration of drugs increased GIP for SW-48 to 93.5%.
Conclusion: C6-Cer appears to have direct inhibitory properties, especially on KRAS Mut cells. When added to Ox, 5-FU and Cet, C6-Cer reversed the apparent insensitivity of KRAS Mut to Cet. Also, the study showed C6-Cer can provide additional synergism to their cytostatic properties in KRAS WT CRC cell lines. The effect of isolated C6-Cer on KRAS Mut raises possibility of a different pathway that could bypass EFGR pathway.

Keywords:

C6-Cer; Cet; Crc; KRAS

Cite the Article:

Menendez A, Haidemenos G, Curzake D, Luo L, Wanebo H. C6-Ceramide (C6- Cer) to Induce Sensitivity to Cetuximab (Cet) in KRAS Mutant Colorectal Cancer (Crc). Clin Oncol. 2016; 1: 1034.