Review of three-dimensional spheroid culture models of gynecological cancers for photodynamic therapy research.

Photodynamic therapy (PDT) is a specific cancer treatment with minimal side effects. However, it remains challenging to apply PDT clinically, partially due to the difficulty of translating research findings to clinical settings as the conventional 2D cell models used for in vitro research are accepted as less physiologically relevant to a solid tumour. 3D spheroids offer a better model for testing PDT mechanisms and efficacy, particularly on photosensitizer uptake, cellular and subcellular distribution and interaction with cellular oxygen consumption. 3D spheroids are usually generated by scaffold-free and scaffold-based methods and are accepted as physiologically relevant models for PDT anticancer research. Scaffold-free methods offer researchers advantages including high efficiency, reproducible, and controlled microenvironment. While the scaffold-based methods offer an extracellular matrix-like 3D scaffold with the necessary architecture and chemical mediators to support the spheroid formation, the natural scaffold used may limit its usage because of low reproducibility due to patch-to-patch variation. Many studies show that the 3D spheroids do offer advantages to gynceologcial cancer PDT investigation. This article will provide a review of the applications of 3D spheroid culture models for the PDT research of gynaecological cancers.

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

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.