Radiotherapy Enhancement with Electroporation in Human Intestinal Colon Cancer HT-29 Cells

Background: The efficiency of radiotherapy for tumors can be enhanced with different radiosensitizers. Previous studies have shown that electroporation (EP) can sensitize some cancer cell lines to ionizing radiation (IR). HT-29 is a radiation resistant colorectal cancer cell line, representative of a cancer type which is the second cause of cancer mortalities in developed countries. The present study aimed to evaluate radiosensitizing effects of EP on HT-29 cells in vitro exposed to 6 MV X-ray photon beams. Methods: HT-29 cells were exposed to a 6 MV X-ray photon beam as the control or to a combination of electroporation and irradiation. The response of cells was evaluated by colony formation assay and survival curves. Results: The survival fraction of the HT-29 cells was significantly decreased by electroporation prior to radiotherapy. A single electric pulse increased colorectal HT-29 cancer cell sensitivity to megavoltage radiation by a factor of 1.36. Conclusion: Our findings showed that EP before radiotherapy can significantly enhance tumor cell sensitivity. This combined treatment modality should be assessed for its applicability in clinic settings for employment against radioresistant cancers. However, to facilitate achieving this goal, many different tumors with a broad range of radiosensitivities should be evaluated.

Gold nanoparticles and electroporation impose both separate and synergistic radiosensitizing effects in HT-29 tumor cells: an in vitro study.

BACKGROUND AND OBJECTIVE: Radiation therapy (RT) is the gold standard treatment for more than half of known tumors. Despite recent improvements in RT efficiency, the side effects of ionizing radiation (IR) in normal tissues are a dose-limiting factor that restricts higher doses in tumor treatment. One approach to enhance the efficiency of RT is the application of radiosensitizers to selectively increase the dose at the tumor site. Gold nanoparticles (GNPs) and electroporation (EP) have shown good potential as radiosensitizers for RT. This study aims to investigate the sensitizing effects of EP, GNPs, and combined GNPs-EP on the dose enhancement factor (DEF) for 6 MV photon energy. METHODS: Radiosensitizing effects of EP, GNPs, and combinations of GNPs-EP were comparatively investigated in vitro for intestinal colon cancer (HT-29) and Chinese hamster ovary (CHO) cell lines by MTT assay and colony formation assay at 6 MV photon energy in six groups: IR (control group), GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR. RESULTS: Treatment of both cell lines with EP, GNPs, and combined GNPs-EP significantly enhanced the response of cells to irradiation. However, the HT-29 showed higher DEF values for all groups. In addition, the DEF value for HT-29 cells for GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR was, respectively, 1.17, 1.47, 1.36, 2.61, and 2.89, indicating synergistic radiosensitizing effect for the GNPs (24 h)+EP+IR group. Furthermore, the synergistic effect was observed just for HT-29 tumor cell lines. CONCLUSION: Combined GNPs-EP protocols induced synergistic radiosensitizing effect in HT-29 cells, and the effect is also tumor specific. This combined therapy can be beneficially used for the treatment of intrinsically less radiosensitive tumors.

Enrichment of skin-derived neural precursor cells from dermal cell populations by altering culture conditions.

BACKGROUND: As stem cells play a critical role in tissue repair, their manipulation for being applied in regenerative medicine is of great importance. Skin-derived precursors (SKPs) may be good candidates for use in cell-based therapy as the only neural stem cells which can be isolated from an accessible tissue, skin. Herein, we presented a simple protocol to enrich neural SKPs by monolayer adherent cultivation to prove the efficacy of this method. METHODS: To enrich neural SKPs from dermal cell populations, we have found that a monolayer adherent cultivation helps to increase the numbers of neural precursor cells. Indeed, we have cultured dermal cells as monolayer under serum-supplemented (control) and serum-supplemented culture, followed by serum free cultivation (test) and compared. Finally, protein markers of SKPs were assessed and compared in both experimental groups and differentiation potential was evaluated in enriched culture. RESULTS: The cells of enriched culture concurrently expressed fibronectin, vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors as compared to control culture. In addition, they possessed a multipotential capacity to differentiate into neurogenic, glial, adipogenic, osteogenic and skeletal myogenic cell lineages. CONCLUSIONS: It was concluded that serum-free adherent culture reinforced by growth factors have been shown to be effective on proliferation of skin-derived neural precursor cells (skin-NPCs) and drive their selective and rapid expansion.