Effect of Foslip® mediated photodynamic therapy on 5-fluorouracil resistant human colorectal cancer cells

Abstract

Colorectal cancer (CRC) is the commonest cancer in Hong Kong and is often treated with 5-fluorouracil (5-FU). However the clinical application of 5-FU was limited by drug resistance in CRC. Photodynamic therapy (PDT) is a novel treatment combating CRC via the combination of photosensitizer, molecular oxygen and light activation. In this study, 5-FU resistant HT29 (HT29FU) was established and its susceptibility to Foslip® PDT tested. Effect of 5-FU to HT29 cells was measured via qPCR. Efficacy of Foslip® PDT on HT29 and HT29FU cells were measured via photosensitizer uptake, cellular localization, cytotoxicity, cell cycle distribution and signal proteins expression. 5-FU significantly induced ABCB1 mRNA expression in HT29 cells; whereas with a 24 fold increase in HT29FU cells. Both cells responded similarly to Foslip® PDT, with the inhibitory concentration IC₂₀, IC₅₀ and IC₇₀ achieved at 1 ng/mL, 2 ng/mL and 5 ng/mL with 2 J/cm² light activation respectively. Foslip® PDT triggered apoptosis and reduced JNK protein expression at IC₇₀ on both cells. Effect of Foslip® PDT on HT29 cells was independent to 5-FU resistance properties. Therefore, Foslip® PDT could be a potential treatment for 5-FU resistant cancer patients. Further investigations on the Foslip® PDT mediated molecular changes in HT29FU cells deserve to be explored.

Keywords: 5-FU resistance; Foslip®; HT29; MAPK signal pathway.