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English Title

Sorafenib and Colon Cancer

Keywords

Sorafenib, Colon carcinoma, Apoptosis, ROS, Cell motility

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

ABSTRACT: Sorafenib, a kinase inhibitor, is among the approved drugs for the treatment of radioactive iodine resistant thyroid carcinoma, primary kidney and liver cancers. Reported targets of Sorafenib include VEGFR, Raf family, and PDGFR belonging to the general class of tyrosine kinases. Blocking growth signals in kidney and breast cancers underlie one of the mechanisms of Sorafenib antitumor effects’ leading to cell death. We hereby examine the effect of Sorafenib on human colon carcinoma cell-line HCT116. We also investigate the possible role of p53 in mediating this effect using mutant HCT116 p53-/- cells. Cultured wild and mutant cells are treated with Sorafenib (0-75µM) for 24 hr. This is followed by assessing the viability of cells using MTT and trypan blue exclusion assays. We also examined if Sorafenib mode of action is mediated by ROS. Levels of ROS were determined in the presence and absence of antioxidants using the colorimetric NBT assay. Our preliminary results show a concentration dependent decrease in viability (trypan blue) with an estimated EC50 of 10 and 25 µM for HCT116 and HCT116 p53-/- respectively. Compared to trypan blue, MTT results were similar in case of HCT116 p53-/- but were significantly different with HCT116. Furthermore we obtained a significant increase in level of ROS of: 37.11% and 31.30% for HCT116 and HCT116p53-/- respectively. However, 2 hours pre-incubation of cells with antioxidants, Trolox, N-acetylcysteine (NAC), and catalase, prior to Sorafenib treatment, exerted no different effect. No restoration of viability or decrease in generated ROS level was noted except when pre-incubated with NAC. Our preliminary findings show that Sorafenib action is independent of ROS level and p53 expression and further investigations on the mechanism(s) of Sorafenib action are ongoing.

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